Oral compositions comprising edible oils and vitamins and/or minerals and methods for making oral compositions

ABSTRACT

The present invention provides oral dosage compositions, and methods of making thereof, which contain an edible oil, preferably containing an omega-3 fatty acid, and admixed therein one or more water soluble vitamins and/or minerals, for example vitamins B6, B9, and/or B12. The present invention also provides a method of making the composition comprising mixing the edible oil and one or more water-soluble vitamins and/or minerals to form a suspension or emulsion of the water-soluble vitamins and/or minerals in the edible oil. The mixture can be inserted into capsules, gelcaps, or caplets for oral consumption. An additional aspect of the invention is that the edible oil can coat particles of the water-soluble vitamins and/or minerals, which may preferably provide the vitamins and/or minerals improved absorption in the body due to increased resistance to degradation in the acidic environment of the stomach.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention is directed to methods and compositions thatcombine nutritional, health and/or medical benefits provided to mammalsby edible oils, particularly by omega-3 fatty acids, with nutritional,health and/or medical benefits provided to mammals by vitamins andminerals, particularly by β vitamins.

The present invention relate to compositions for an oral administrationto mammals comprising one or more edible oils and one or more watersoluble vitamins and/or minerals. The one or more edible oils preferablyinclude one or more omega-3 fatty acids, and are uniformly combined. Theone or more vitamins and/or minerals preferably include one or morewater-soluble and oil-insoluble B vitamins, and more preferably includevitamin B6 (pyridoxine), vitamin B9 (folic acid or folate) and/orvitamin B12 (cyanocobalamin, cobalamin, cobalamin bound to recombinantintrinsic factor (rhIF) and/or reduced forms of cobalamin), which may bepresent in any combination. The one or more vitamins and/or mineralspreferably are present in a solid state, and in the form of a uniformmixture, and are uniformly suspended within the one or more edible oils,or are present within an emulsion (wherein such oil phase includes theone or more edible oils).

The present invention also relates to methods for producing suchcompositions, and to methods for using such compositions to provide oneor more nutritional, health and/or medical benefits to a mammal, or toenhance one or more of such benefits in a mammal.

Examples of water-soluble vitamins include the B-vitamins, and moreparticularly, at least one of vitamin B6, vitamin B9, and vitamin B12,or any combination thereof. The water-soluble vitamins and/or mineralsare optionally present in a solid-state form, such as an amorphouspowder or a milled material, for example, a finely milled crystallinematerial, but can also be present in solution as part of an emulsion ofan aqueous solution and the edible oils.

Water-soluble vitamins and/or minerals present in solid form incompositions of the invention preferably become at least temporarilysuspended in, and coated with, one or more edible oils. For example, inone embodiment of the invention, a solid form including a uniformmixture of the water-soluble B vitamins B6, B9 and B12 is coated with,and suspended within, an omega-3 oil. While not wishing to be bound bytheory it is presently believed that, as a result of the vitamins and/orminerals being coated by an edible oil, compositions within the presentinvention may have an enhanced ability to transport water-solublevitamins and/or minerals through the stomach of a mammal, whichgenerally is a highly acid environment that is maintained by thesecretion of hydrochloric acid, without being degraded and, thus,permitting some or all of the water-soluble vitamins and/or minerals tobe delivered to the intestinal tract, where they can be absorbed anddelivered to other parts of the mammal's body, such as the capillaries,the lymphatic system and the circulatory system, and produce abeneficial effect.

Compositions within the invention may be employed to provide, orenhance, nutritional, medical and/or other health benefits to mammals,whether in satisfactory health or suffering from one or more conditions,illnesses, diseases or disorders, including depression, dementia,Alzheimer, schizophrenia, rheumatoid arthritis, non-specific arthritis,osteoarthritis, osteoporosis, diabetes, neurological development anddegeneration, allergic and immunologic disorders, cancer, pregnancy,lactating women, and disease states effected or characterized byelevated blood pressure, low HDL, arrhythmia, elevated levels ofhomocysteine, triglycerides and c-reactive protein and low levels of thecomponents of the invention.

Nutritional and Medical Benefits Provided by Edible Oils and Fatty Acids

Edible fats and oils generally provide nutritional and health benefitsto mammals. Fats are one of the three main classes of food,.and are themost concentrated form of metabolic energy available to humans. Fats andoils are sources of essential fatty acids, an important dietaryrequirement, as well as other nutritious fatty acids.

Clinical studies have shown that certain edible oils containing DHA (an“omega-3” fatty acid) and other fatty acids can provide significantmedical benefits to mammals, particularly to human beings. For example,both omega-3 and omega-6 fatty acids are associated with a lower risk ofcoronary heart disease. [Frank B. Hu, M. D. et al., “Types of DietaryFat and Risk of Coronary Heart Disease: A Critical Review,” J Am CollNutr. 20(1): 5-19 (2001).]

Other publications that discuss the nutritional, health and/or medicalbenefits provided by edible oils include Elda Hauschildt,“Alpha-Linolenic Acid may help Prevent Heart Disease,” Am J Clin Nutr.Vol. 75, 221-227 (2002); Yvonne E. Finnegan et al., “Plant- andMarine-Derived n-3 Polyunsaturated Fatty Acids have Differential Effectson Fasting and Postprandial Blood Lipid Concentrations and on theSusceptibility of LDL to Oxidative Modification in ModeratelyHyperlipidemic Subjects,” Am J Clin Nutr., Vol. 77, 783-795 (2003);Rozenn N. Lemaitre et.al., “n-3 Polyunsaturated Fatty Acids, FatalIschemic Heart Disease, and Nonfatal Myocardial Infarction in OlderAdults: the Cardiovascular Health Study,” Am J Clin Nutr., Vol. 77,319-325 (2003); Dayong Wu et al., “Effect of Dietary Supplementationwith Black Currant Seed Oil on the Immune Response of Healthy ElderlySubjects,” Am J Clin Nutr. Vol. 70(4), 536-543 (1999); Frank B. Hu etal., “Dietary Intake of α-Linolenic Acid and Risk of Fatal IschemicHeart Disease Among Women,” Am J Clin Nutr. Vol. 69, 890-897 (1999); andE H Temme et al., “Comparison of the Effects of Diets Enriched inLauric, Palmitic, or Oleic Acids on Serum Lipids and Lipoproteins inHealthy Women and Men,” Am J Clin Nutr., Vol 63, 897-903 (1996).

Fatty acids, such is “omega-3” fatty acids (also known as “n-3” fattyacids), “omega-6” fatty acids, “omega-9” fatty acids and essential fattyacids are generally present in high levels in various edible oils.“Omega-3 fatty acids” are the n-3 family of polyunsaturated fatty acids,and are called “n-3 fatty acids” because the first double bond occurs inthe third carbon bond counting from the end or omega position of thefatty acid. Omega-3 fatty acids have many nutrition, health and/ormedical benefits associated with them, and thus, can provide numerousbeneficial effects to human beings and a wide variety of animals thatingest them, whether the consumers are healthy or have one or morediseases or disorders. Although omega-3 fatty acids can be obtained fromother sources, such as plant oils, fish have a unique ability to providehigh levels of various specific fatty acids, such as omega-3 fatty acidsdocosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Omega-3fatty acids include, for example, docosahexaenoic acid (DHA),docosapentaenoic acid, alpha-linolenic acid (ALA), eicosapentaenoic acid(EPA), eicosatetraenoic acid, moroctic acid and heneicosapentenoic acid.Omega-3 fatty adds are precursors of eicosanoids (prostaglandins,thromboxanes and leukotrienes), which are signal substances (cellmessengers) that have a widely different effect upon biologicalactivity. Many of these signal substances regulate physiological andimmunological reactions.

Omega-3 fatty adds have been shown to be beneficial in the prevention ofcardiovascular pathology, the reversal of atherosclerosis, theinhibition of tumor formation and the development and the regulation ofserum cholesterol. Prospective cohort studies and secondary preventiontrials have provided strong evidence that an increasing intake ofn-fatty acids from fish or plant sources substantially lowers risk ofcardiovascular mortality. [Frank B. Hu, M. D. et al., “Types of DietaryFat and Risk of Coronary Heart Disease: A Critical Review,” supra.]Other research suggests the therapeutic value of oils rich in omega-3unsaturated fatty acids for disorders related to blood hyperviscosity,including the lowering of serum cholesterol and the suppression orreduction of plasma triglycerides, inflammatory autoimmune disorders,tumors and various other disorders. [D. F. Horrobin, “Clinical uses ofEssential Fatty Acids,” Eden. Press, London, 1982.] The omega-3 fattyacids also suppress the production of the proinflammatory cytokinestumor necrosis factor (TNF), particularly TNF alpha, interleukin-1(IL-1) and thromboxanes. The protective effects of n-3 fatty acids arelikely a result of multiple mechanisms, including reducing triglyceridelevels, reducing platelet aggregation and antiarrhythmic effects.

Omega-3 fatty acids are also essential for the normal development of anunborn baby's brain, especially during the third trimester, when thesize of a baby's brain increases threefold. If a baby's mother fails tohave a sufficient quantity of omega-3 fatty acids in her diet, the fetuswill generally depend upon the mother's brain tissue and tissue storageof these omega-3 fatty acids. Lab tests have shown that new mothers haveapproximately one half of the normal blood levels of omega-3 fattyacids.

Linolenic acid, a polyunsaturated fatty acid having three double bonds,is a precursor to EPA and DHA, and is considered to be a dietaryessential fatty acid. Because the body is not capable of synthesizinglinolenic acid, it must be acquired from a dietary source, such as foodor supplements.

DHA is an omega-3 long-chain fatty acid that is the primary structuralfatty acid in the gray matter of the brain, and in the retina of theeye, and accumulates during the fetal period and during the first yearafter birth. DHA is essential for normal visual and neurological(nervous system) development in infants, and for normal brain and eyefunction in adults. It is necessary for brain and eye development,growth and learning ability in children. [A. P. Simopoulos, “Omega-3Fatty Acids in Health and Disease and in Growth and Development,”American Journal of Clinical Nutrition 54, No. 3, 438-463 (1991).]

The human body only synthesizes small quantities of DHA. As a result, itis necessary to obtain DHA from dietary sources. The primary source ofDHA is fatty fish, such as mackerel, salmon, herring, sardines, blackcod, anchovies and albacore tuna, and oils from the tissues of suchfish.

DHA and EPA, which is associated with vascular regeneration, can altereicosanoid and cytokine production, providing an improvedimmunocompetence (strengthening immune system activity) and a reducedinflammatory response to injury. The contribution of DHA and EPA toreducing the incidence of numerous inflammatory/circulatory disorders,cardiac problems, premature births, cognitive ability in children andmental well being has been well documented.

ALA is an essential omega-3 fatty acid for humans. Adequate intake ofALA and long-chain omega-3 fatty acids is especially important forinfants, young children and patients requiring parenteral and enteralnutrition. Experimental studies have suggested an antiarrhythmic effectof ALA, and beneficial effects of ALA on cardiovascular disease. [FrankB. Hu, M. D. et al., “Types of Dietary Fat and Risk of Coronary HeartDisease: A Critical Review,” supra.]

“Omega-6” fatty acids include gamma-linolenic acid (GLA), which ispresent in Black Current Seed Oil, linoleic acid, which is present inmany vegetable oils, and arachidonic acid, which is present in manyanimal fats and in algae oil. GLA is an n 18:3 omega-6 polyunsaturatedfatty acid that has been used in the amelioration of various diseases,such as eczema, rheumatoid arthritis and premenstrual syndrome, and thathas been shown to improve the effectiveness of cancer chemotherapy.Arachidonic acid (ARA or AA) is an omega-6 polyunsaturated fatty acidthat has been shown to play a role in early neurological and visualdevelopment and is a precursor in the biosynthesis of someprostaglandins.

“Omega-9” fatty acids include, for example, oleic acid, which is presentin sunflower oil, olive oil, avocados, canola oil and in many animalfats.

Marine oils (including “fish oils”) are oils that are obtained fromaquatic lifeforms, either directly or indirectly, particularly from oilyfish. Marine oils include, for example, herring oil, cod oil, anchovyoil, tuna oil, sardine oil, menhaden oil and algae oil. Fish that areemployed to produce marine oils include, for example, farm-raised orwild, fresh-water or salt-water, fish and shellfish, such as herring,salmon, salmonoids, gadoids, shrimp, cod, carp, tilapia, perch, trout,sturgeon, krill, tuna, flat fish, anchovies, sardines, menhaden, shrimp,Mackerel, eels and seals. Marine oils may also be obtained from marineorganisms, such as calanus (Calanus finmarchicus), a 3-4 mm copepod,algae and microalgae, for example, diatoms and dinoflagellates. Peru iscurrently the world's largest producer of fish oil.

Although omega-3 fatty acids can be obtained from other sources, such asplant oils, fish have a unique ability to provide high levels of theomega-3 fatty acids DHA and EPA. Fish and fish oil are also sources ofthe “omega-3” fatty acids docosapentaenoic acid, eicosatetraenoic acid,moroctic acid and heneicosapentenoic acid. Marine oils having a total“omega-3” fatty acid content of greater than about 20 weight percentinclude those derived from menhaden oil, herring, capelin, anchovy, codliver, salmon oil, sardine oil and mixtures thereof. Oils containingomega-3 fatty acids, such as marine oils and DHA, are also referred toas “omega-3” oils or “n-3” oils.

A low rate of cardiovascular disease in populations that have a highintake of fish, such as Alaskan Native Americans, Greenland Eskimos andJapanese living in fishing villages, suggests that fish oil may beprotective against artherosclerosis. [Frank B. Hu, M. D. et al., “Typesof Dietary Fat and Risk of Coronary Heart Disease: A Critical Review,”supra.] Additionally, research into the blood chemistry of Eskimos, whoconsume large quantities of fish, showed low levels of low-densitylipoproteins (LDL cholesterol) and high levels of high-densitycholesterol (HDL cholesterol) in the blood despite a rich diet of fattyfish and seals. [Dyerberg et al., “Fatty Acid Composition of PlasmaLipids in Greenland Eskimos,” American Journal of Clinical Nutrition 28,958-966 (1975).]

It is known that oral administration of fish oil, which contains omega-3fatty acids, has beneficial effects on cardiovascular function, brainfunction and has other health benefits. One article reports “asignificant, graded, independent inverse association between base-linefish consumption and the 30-year risk of fatal myocardial infarction,particularly nonsudden death from myocardial infarction [that] accountedfor the [observation of] lower rates of death from all coronary causes,all cardiovascular causes, and all causes in-association with higherfish consumption . . . ” [Daviglus, M. L., et al., N Engl J Med 1997;336(15):1046-53.]

Another study found that “dietary intake of omega-3 fatty acids,approximately 1.5 g/l for 2 years, modestly mitigated the course ofhuman coronary atherosclerosis, as assessed by angiography. Fewercardiovascular events were noted.” [von Schacky, C., et al, Ann InternMed. 1999; 130:554-62.] Yet another study found that omega-3 fatty acidsfound in fish oil reduced the risk of sudden death in men withoutevidence of prior cardiovascular disease. [Albert, C. M., et al., N EnglJ Med 2002; 346(15):1113-18.]

There is growing evidence to suggest that fish oil may improveendothelial dysfunction, an early marker of atherosclerosis. In vitrostudies have consistently shown that n-3 fatty adds decrease expressionof adhesion molecules on the endothelium, and also decreaseleukocyte/endothelium interations. Further, clinical experimentalstudies have shown that n-3 fatty acid supplementation improvesendothelial-dependent vasomotor function. [Frank B. Hu, M. D. et al.,“Types of Dietary Fat and Risk of Coronary Heart Disease: A CriticalReview,” supra.]

Various modified or unmodified fungi, such as filamentous fungi, alsohave an ability to produce lipids having high levels of vitamins, suchas GLA. Modified fungi have been employed to ferment DHA oil. Fungi canbe isolated from soil and subsequently fermented using known techniquesand conventional shake flasks or fermentation systems.

Many plant oils (including vegetable oils and plant seed oils), such asEvening Primrose oil, Black Currant seed oil, Borage oil, Borage seedoil, safflower oil, sunflower oil, peanut oil, olive oil, corn oil,soybean oil, coconut oil, palm oil, palm kernel oil, rapeseed oil,flaxseed (linseed) oil and cotton seed oil, contain high levels of fattyacids, such as GLA, as well as other fatty acids. For example, flaxseedoil, rapeseed oil and soybean oil contain a large quantity of ALA (about20% in flaxseed oil and about 7% in unhydrogenated soybean oil). GLA ispresent in Evening Primrose oil, Black Currant seed oil and Borage seedoil, with the highest level of GLA being present in Borage seed oil.Safflower oil and sunflower oil are rich in linoleic acid. Olive oilcontains a significant amount of oleic acid.

Numerous metabolic studies have shown strong cholesterol-loweringeffects for vegetable oils that are rich in linoleic oil whensubstituted for dietary saturated fat. In addition, animal studies havesuggested an anti-arrhythmic effect when sunflower oil (rich in linoleicacid) was consumed. [Frank B. Hu, M. D. et al., “Types of Dietary Fatand Risk of Coronary Heart Disease: A Critical Review,” supra.]

Plant oils can be extracted from plants or seeds using techniques thatare known by those of skill in the art. For example, the highest qualityBorage seed oil is generally extracted without hexane or the use ofother chemical solvents. Rather, the Borage seed oil is “cold processed”using an expeller-press method of extraction, which simply squeezes theoil out from the seed without the use of heat.

With respect to neurological function, Morris, M. C., et al., ArchNeurol 2003: 60: 940-6, have shown that the omega-3 polyunsaturatedfatty acids have “profound effects on membrane functions, leading tochange in nerve conduction, neurotransmitter release, neurotransmitterreuptake, and postsynaptic transmitter effects. A large number of animalstudies have demonstrated that dietary n-3 fatty acids increasedlearning acquisition and memory performance . . . .” See also, Horrocks,L. A. and Young, K. Y., Pharmacological Research 1999; 40(3):211-25(“Low levels of DHA are also associated with senile dementia (Alzheimerdisease) and schizophrenia.” “Chronic alcohol intoxication depletes DHAfrom membranes of the neurons, leading to the common secondarydepression in alcoholism.”).

Zanarini, M. C. and Frankenburg, F. R, Am J Psychiatry 2003; 160: 167-9,reports results from a double-blind, placebo-controlled study that are“consistent with the findings of recent reports concerning omega-3-fattyacids as an effective adjunctive treatment for bipolar disorder andrecurrent depression.”

Thus, there is substantial evidence that omega-3 fatty acids canbeneficially affect a variety of diseases. See e.g., Conner, W. E., Am JClin Nutt 2000; 71(suppl):171S-5S (omega-3 fatty acids “favorably affectatherosclerosis, coronary heart disease, inflammatory disease, andperhaps even behavioral disorders.”).

Nutritional and Medicinal Benefits Provided by B-Vitamins and OtherWater-Soluble Vitamins and Minerals

High levels of homocysteine have been reported to be associated withcardiovascular diseases. Refsum, H: and Ueland, P. M, Annu Rev Medicine1998; 49:31-62 report that “[a]n elevated level of total homocysteine(tHcy) in blood, denoted hyperhomocysteinemia, is emerging as aprevalent and strong risk factor for atherosclerotic vascular disease inthe coronary, cerebral, and peripheral vessels, and for arterial andvenous thromboembolism.” Similarly, Schnyder, G., et al. N Engl J Med2001: 345(22):1593-1600, report that the level of plasma homocysteinecan be reduced significantly with a daily dose of folic acid in anamount of at least 500 micrograms, in combination with vitamin B6(pyridoxine) and vitamin B12 (cyanocobalamin, cobalamin, and/or reducedforms of cobalamin). “Roughly one half of US adults on a given dayconsume less than the newly lowered recommended dietary allowance forfolate, and an estimated 88% consume less than the levels needed toproduce low, stable homocysteine levels.” Morrison, H. I., et al. SerumFolate and Risk of Fatal Coronary Heart Disease JAMA 1996;275(24):1893-6.

Vitamin B9 (folic acid/folate) is thought to be crucial for proper brainfunction and plays an important role in mental and emotional health. Itaids in the production of DNA and RNA, the body's genetic material, andis especially important during periods of high growth, such as infancy,adolescence and pregnancy. Folic acid also works closely together withvitamin B12 to regulate the formation of red blood cells and to helpiron function properly in the body.

Vitamin B9 works closely with vitamins B6 and B12 as well as with thenutrients betaine and S-adenosylmethionine (SAM) to control blood levelsof the amino acid homocysteine. Elevated levels of this substance appearto be linked to certain chronic conditions such as heart disease and,possibly, depression and Alzheimer's disease. Some researchers have evenspeculated that there is a connection between high levels of this aminoacid and cervical cancer, but the results of studies regarding this havebeen inconclusive.

Vitamin B12 (cyanocobalamin, cobalamin, cobalamin bound to recombinantintrinsic factor (rhIF) and/or reduced forms of cobalamin) functions asa methyl donor and works with folic acid in the synthesis of DNA and redblood cells and is vitally important in maintaining the health of theinsulation sheath (myelin sheath) that surrounds nerve cells. Theclassical vitamin B12 deficiency disease is pernicious anemia, a seriousdisease characterized by large, immature red blood cells. It is nowclear though, that a vitamin B12 deficiency can have seriousconsequences long before anemia is evident. Many elderly people are alsodeficient because their production of the intrinsic factor needed toabsorb the vitamin from the small intestine decline rapidly with age.

Vitamin B12 plays an important role in maintaining a low bloodconcentration of homocysteine by participating in reactions that recyclehomocysteine into methionine. In cases of a deficiency of vitamin B12the conversion of homocysteine to methionine is inhibited. The resultingraised level of homocysteine has been estimated to be a greater riskfactor and predicator for cardiovascular diseases than an increasedlevel of cholesterol, high blood pressure, cigarette smoking, andelevated lipoproteins and hypertension. A B12 deficiency has also beensuggested to be an independent risk factor for neural tube birthdefects. Neural tube defects (NTDs) are a failure of closure of theneural tube, which includes the spinal cord and the brain, and is amongthe most devastating of all birth defects. A deficiency of vitamin B12is thought to result in a lack of methionine, which is the soleprecursor to the “universal methylator” (S-adenosylmethionine).S-adenosylmethionine participates in almost all methylation processes inthe human body. Mack of S-adenosylmethionine slows the growth and/orclosure of the neural tube and thereby increase the risk of NTDs. Lowerplasma levels of vitamin B12 has also been associated with breastcancer. Vitamin B12, along with folate and vitamin B6, functions as acoenzyme in the building of components for DNA synthesis. Inadequatelevels of vitamin B12 may cause misincorporation of uracil, normallyfound in RNA, into DNA, which may result in chromosome breaks anddisruption of DNA repair. Additionally a deficiency of vitamin B12 maycause aberrant DNA methylation, which has been observed in human tumors.Vitamin B12 deficiency is particularly associated with cognitiveimpairment and widespread pathology in the central nervous system in theelderly. In cells vitamin B12 is converted to coenzymes, which influencebrain function through the one carbon metabolism/methylation cycle.Vitamin B12 is required for the synthesis of methionine andS-adenosylmethionine, which the brain relies on to metabolizehomocysteine. Furthermore, S-adenosylmethionine dependant reactionsinclude the formation of neurotransmitters, phospholipids and myelin.Thus, vitamin B12 deficiency may cause nervous system dysfunction in theelderly. A severe and progressive consequence of a deficiency of vitaminB12 is the degeneration of the spinal cord. Classical symptoms includesymmetrical parasthesias in the hands and feet leading to numbness,muscle weakness and paralysis.

Need for a Dosage Form Incorporating Both Fatty Acids and B-Vitamins

In view of the significant nutritional, medical and/or other healthbenefits provided by many edible oils, such as the omega-3 fatty acidsDHA, EPA and ALA, and by water-soluble vitamins and/or minerals, such asB-vitamins, it would be beneficial to provide dosage forms for oraladministration that include one or more edible oils and one or moreB-vitamins that properly disintegrate, thereby allowing the edible oilsand B-vitamins to become bioavailable, that may permit the edible oilsand B-vitamins to be absorbed by the body without being substantiallydegraded in the acidic environment of the stomach, and that may have along shelf life under room temperature conditions. In view of thesebenefits, compositions within the present invention may be effective forimproving cardiovascular function, lowering the incidence of myocardialinfarction, improving cardiac arrhythmia problems and/or loweringelevated homocysteine levels which, in turn, may have the benefit oflowering the incidence of heart disease and/or depression.

Description of the Related Art

The Physicians' Desk Reference (49^(th) Edition, 1995, and 54^(th)Edition, 2000) describes a prenatal vitamin and mineral tablet marketedby Lederle Laboratories (Wayne, N.J.) under the trademark name Materna®(pages 1264 and 1534, respectively).

U.S. Pat. No. 5,494,678 discloses multi-vitamin and mineral supplementsfor incorporation into tablets, powders, granules, beads, lozenges,capsules and liquids, and administration to a pregnant woman during herfirst, second and third trimesters of pregnancy. The supplements containspecific regimens of a calcium compound, vitamin D, folic acid, vitaminB12, vitamin B6, and vitamin B1.

U.S. Pat. No. 5,571,441 discloses nutritional supplement compositionscontaining vitamins, minerals, central nervous system bracers, such ascaffeine, and flavenols, that are coadministered in the form of a tabletor capsule, as a powder, or as a liquid form.

U.S. Pat. No. 5,869,084 discloses multi-vitamin and mineral supplementsfor administration to lactating, non-lactating (but not pregnant) andmenopausal women in the form of tablets, powders, granules, beads,lozenges, capsules or liquids.

U.S. Pat. No. 5,906,833 discloses nutritional supplements that containvitamins.

SUMMARY OF THE INVENTION

The present invention provides compositions for an oral administrationto a mammal that include one or more edible oils and one or more otherwater-soluble vitamins and/or minerals, and that generally properlydisintegrate, thereby allowing the edible oils and/or water-solublevitamins and/or minerals to become bioavailable, permitting thewater-soluble vitamins and/or minerals to be absorbed by the bodywithout being substantially degraded in the acidic environment of thestomach, and have a long shelf life under room temperature conditions.

In one aspect, the present invention provides compositions for an oraladministration to a mammal comprising:

-   -   (a) one or more water-soluble vitamins and minerals in a        combined amount that is effective for providing or enhancing a        nutritional, medical or other health benefit to a mammal,        wherein the one or more water-soluble vitamins and/or minerals        are in a form that is capable of being mixed with one or more        edible oils;    -   (b) one or more edible oils in a combined amount that is        effective for permitting the one or more water-soluble vitamins        and/or minerals to be mixed with the one or more edible oils;        and    -   (c) one or more anhydrous diluents for the powder phase    -   (d) optionally, one or more antioxidant agents in a combined        amount that is effective for preventing or reducing an        oxidation, degradation or other decomposition of the one or more        water-soluble vitamins, and/or minerals, or the one or more        edible oils;        After compositions within the invention are consumed by a        mammal, at least some of the water-soluble vitamins and/or        minerals present therein generally have an enhanced ability to        travel through an acidic environment of a stomach of the mammal        without being partially or fully degraded and into an intestinal        tract of the mammal, and to be absorbed into the mammal's body,        in comparison with other compositions for oral administration        that contain the same water-soluble vitamins and/or minerals; or        wherein the compositions have an enhanced stability and/or shelf        life in comparison with other compositions for oral        administration that contain the same water-soluble vitamins        and/or minerals.

In another aspect, the present invention provides compositions for anoral administration to a mammal comprising:

(a) one or more solid-state particles of one or more water solublevitamins or minerals in a combined amount that is effective forproviding or enhancing a nutritional, medical or other health benefit tothe mammal;

(b) one or more edible oils that include one or more fatty acids,wherein the one or more fatty acids are omega-3 fatty acids, omega-6fatty acids or omega-9 fatty acids, and wherein the one or more fattyacids are in a combined amount that is effective for permitting thesolid state particles to be at least temporarily suspended therein;

wherein the solid state particles are admixed with the one or moreedible oils or at least temporarily suspended therein.

In another aspect, the present invention provides compositions for anoral administration to a mammal comprising:

(a) one or more solid-state particles of one or more water solublevitamins, wherein the one or more water soluble vitamins are vitamin B6,vitamin B9 or vitamin B12, or a combination thereof, and wherein the oneor more water soluble vitamins are in a combined amount that iseffective for providing or enhancing a nutritional, medical or otherhealth benefit to the mammal;

(b) one or more edible oils including one or more omega-3 fatty acids ina combined amount that is effective for providing or enhancing anutritional, medical or other health benefit to the mammal.

wherein the solid-state particles are mixed with the one or more edibleoils or at least temporarily suspended therein.

In another aspect, the present invention provides compositions for anoral administration to a mammal comprising:

(a) one or more water soluble vitamins or minerals, or combinationthereof, in a combined amount that is effective for providing orenhancing a nutritional, medical or other health benefit to the mammal,wherein the one or more water soluble vitamins or minerals are combinedwith an amount of water that is sufficient to form an aqueous solution;

(b) one or more edible emulsifiers in a combined amount that iseffective to cause or enhance the formation of an emulsion;

(c) one or more edible oils in a combined amount that is effective forforming an oil phase of an emulsion;

wherein the aqueous solution is combined with the one or moreemulsifiers and the one or more edible oils in a manner that forms anemulsion.

In another aspect, the present invention provides a method for preparingcompositions for an oral administration to a mammal comprising thefollowing steps (in any convenient or possible order):

-   -   (a) providing one or more water-soluble vitamins and/or minerals        in a combined amount that is effective for providing or        enhancing a nutritional, medical or other health benefit to a        mammal, wherein the one or more water-soluble vitamins and/or        minerals are, optionally, in a solid-state form and/or capable        of being suspended within one or more edible oils;    -   (b) providing one or more edible oils in a combined amount that        is effective for permitting the one or more water-soluble        vitamins and/or minerals to be at least temporarily suspended        therein;    -   (c) optionally, mixing the one or more water-soluble vitamins        and/or minerals for a period of time and under conditions that        are sufficient to produce a uniform mixture of the one or more        water-soluble vitamins and/or minerals;    -   (d) optionally, mixing the one or more edible oils for a period        of time and under conditions that are sufficient to produce a        uniform mixture of the one or more edible oils; and    -   (e) suspending an amount of the one or more water-soluble        vitamins and/or minerals, or mixture thereof, within an amount        of the one or more edible oils, or mixture thereof, that is        effective for producing a suspension of the one or more        water-soluble vitamins and/or minerals, or mixtures thereof,        within the one or more edible oils, or mixtures thereof.        After the compositions are consumed by a mammal, at least some        of the water-soluble vitamins and/or minerals present therein        generally have an enhanced ability to travel through an acidic        environment of a stomach of the mammal without being partially        or fully degraded and into an intestinal tract of the mammal,        and to be absorbed into the mammal's body, in comparison with        other compositions for oral administration that contain the same        water-soluble vitamins and/or minerals; or wherein the        compositions have an enhanced stability and/or shelf life in        comparison with other compositions for oral administration that        contain the same water-soluble vitamins and/or minerals.

In another aspect, the present invention provides a method for preparingcompositions for an oral administration to a mammal comprising.

(a) providing one or more solid state particles of one or more watersoluble vitamins or minerals, or combination thereof;

(b) providing one or more edible oils including one or more fatty acidsin a combined amount that is effective for permitting the one or morewater soluble vitamins or minerals to be at least temporarily suspendedtherein;

(c) optionally, mixing the one or more water soluble vitamins orminerals, or combination thereof, for a period of time and underconditions that are sufficient to produce a uniform mixture of the oneor more water soluble vitamins or minerals, or combination thereof;

(d) optionally, mixing the one or more edible oils for a period of timeand under conditions that are sufficient to produce a uniform mixture ofthe one or more edible oils;

(e) suspending, at least temporarily, an amount of the one or more watersoluble vitamins or minerals, or combination thereof, within an amountof the one or more edible oils, or combination thereof, that iseffective for producing a suspension of the solid-state particles of theone or more water soluble vitamins or minerals, or combination thereof,within the one or more edible oils, or mixtures thereof;

(f) injecting a resulting suspension into an oral dosage form, whereinthe oral dosage form is hard or soft capsule, gelatin capsule, caplet orgelatin caplet.

In another aspect, the present invention provides a method for preparingcompositions for an oral administration to a mammal comprising:

(a) providing one or more solid-state particles of one or more watersoluble vitamins or minerals or combination thereof;

(b) mixing the solid-state particles in an amount of water that issufficient to form an aqueous solution;

(c) providing one or more edible emulsifiers or a combination thereof;

(d) providing one or more edible oils or combination thereof, includingone or more fatty acids;

(e) optionally, mixing the one or more edible oils or combinationthereof for a period of time and under conditions that are sufficient toproduce a uniform mixture of the one or more edible oils;

(f) mixing the aqueous solution with the one or more edible emulsifiersor combination thereof and the one or more edible oils or combinationthereof under conditions that are sufficient to form an emulsion;

(g) injecting the emulsion into a hollow oral dosage form that is a softor hard capsule, gelatin capsule, caplet or gelatin caplet.

In yet another aspect, the present invention provides a method forenhancing the quantity of one or more water-soluble vitamins and/orminerals that are absorbed by an intestinal tract of a mammal anddelivered to the mammal's body after the mammal consumes one or morewater-soluble vitamins and/or minerals and/or edible oils comprisingadministering to the mammal a composition according to claim 1.

In still another aspect, the present invention provides a method forenhancing the nutrition, health and/or medical condition of a mammalcomprising administering to the mammal an effective amount of acomposition according to claim 1.

In still another aspect, the present invention provides a method forenhancing the nutrition, health and/or medical condition of a mammalcomprising administering to the mammal an effective amount of acomposition according to claim 18.

The water-soluble vitamins and/or minerals, that may be present in thecompositions of the invention may be present alone or in any desiredcombination of two or more water-soluble vitamins and/or minerals. Forexample, the compositions may include the vitamins B6, B9 and B12, orother B vitamins, alone or in any desired combination, and in anydesired quantity. The water-soluble vitamins and/or minerals employed inthe compositions of the invention are, optionally, in solid-state formsand subsequently suspended in one or more edible oils to produce asuspension in which the solid-state vitamins and/or minerals are coatedwith the one or more edible oils. The water-soluble vitamins and/orminerals can also be present in the compositions in the form of anaqueous solution in combination with an emulsifier that forms anemulsion with the one or more edible oils. The compositions of thepresent invention are suitable for an oral administration to a mammal,and are typically provided as gelatin capsules, such as soft-gel orhard-gel capsules, but may be provided in any other suitable oral dosageform as is known by those of skill in the art.

Edible oil suspensions of solid-state B and/or other vitamins and/orminerals can be prepared by mixing powdered (e.g., micronized or milled)vitamins and/or minerals so as to form a substantially uniform mixtureand subsequently suspending such mixture in one or more edible oils, ormixture thereof, to produce a suspension that is preferably homogeneous,and is capable of remaining as a homogenous suspension at least duringthe filling step of processes for preparing gel capsules (or other oraldosage forms) with the suspension so as to maximize content uniformityin the various filled gel capsules (or other oral dosage forms).

The stability of water-soluble vitamins and/or minerals present incompositions within the present invention may generally be enhanced incomparison with other oral dosage forms containing the same or similarwater-soluble vitamins and/or minerals, for example, those that areprepared in a different manner (i.e. those that do not have one or moresolid-state water-soluble vitamins and/or minerals suspended within oneor more edible oils). Such an improved stability generally results inthe compositions of the invention having an enhanced stability and/or alonger shelf life than would otherwise be achievable, and is likely aresult of the solid-state water-soluble vitamins and/or mineralsbecoming coated with the one or more edible oils and, thus, protectedfrom degradation. Further, for the same reasons, compositions within thepresent invention generally result in an enhanced absorption of the Bvitamins, or other water-soluble vitamins and/or minerals, by the bodyof the mammal. The oil coated vitamins and/or minerals may generally bedelivered into the intestinal tract before being substantiallysolubilized, which generally prevents or limits the acidic environmentof the mammal's stomach from fully degrading, or otherwise substantiallydiminishing the effectiveness of, the water-soluble vitamins and/orminerals.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention may be understood more readily by reference to thefollowing detailed description of the preferred embodiments.

For purposes of clarity, various terms and phrases used throughout thisspecification and the appended claims are defined in the manner setforth below. If a term or phrase used in this specification, or in theappended claims, is not defined below, or otherwise in thisspecification, the term or phrase should be given its ordinary meaning

Definitions

The phrase “antioxidant agent” as used herein means an agent that isedible, and that can prevent or reduce an oxidation, degradation and/orother decomposition that would otherwise occur to components oringredients of the compositions of the invention, such as water-solublevitamins, minerals and/or edible oils. Antioxidant agents include, butare not limited to, ascorbyl palmitate, various tocopherol mixtures,acids, such as citric acid and ascorbic acid, herbal extracts, such as aRosemary, Sage, Oregano, Ginger, Marjoram or Rosemary Oleoresinsextract, plant phenols, such as Vanillin, ellagic acid and Resveratrol,and synthetic antioxidants, such as tertiary butylhydroquinone (TBHQ),butylated hydroxyamisole (BHA) or butylated hydroxytoluene (BHT), ormixtures thereof.

The phrase “Daily Reference Value” (DRV) as used herein means a labelreference value set by the U.S. Food and Drug Administration (“FDA”) foruse in declaring the nutrient content of a food on its label orlabeling.

The phrase “Daily Value” (DV) as used herein means a value set by theFDA for assisting consumers in understanding the relative significanceof information about the amount of certain water-soluble vitamins and/orminerals in a food in the context of a total daily diet. This valueassists consumers in comparing the nutritional values of food products.The Daily Value is determined by the FDA by combining the ReferenceDaily Intakes (RDIs) and the Daily Reference Values (RDAs) labelreference values. The term “Daily Value,” thus, refers to the combinedset of label reference values.

The term “edible” as used herein means capable of being eaten, consumedand/or ingested by a mammal without being toxic or otherwise harmful tothe mammal or, if the mammal is pregnant or lactating, to a developingfetus or a breast-feeding baby of the mammal.

The phrase “edible oils” as used herein means oils, or componentsthereof, such as fatty acids, that are edible, and that may be employedin pharmaceutical or other compositions for an oral administration.Edible oils include, but are not limited to, vegetable oils, including,Evening Primrose oil, Black Currant seed oil, Borage oil, Borage seedoil, safflower oil, safflower seed oil, sunflower oil, sunflower seedoil, sesame seed oil, peanut oil, walnut oil, almond oil, olive oil,olive seed oil, avocado oil, avocado seed oil, pumpkin seed oil, cornoil, cod liver oil, soy oil, soybean oil, coconut oil, palm oil, palmkernel oil, rapeseed oil, flaxseed (linseed) oil, cotton seed oil, tungoil, palmolein oil, mustard seed oil, oiticica oil and castor oil, andmarine oils (including “fish oils”), such as those that are obtainedfrom aquatic life forms, either directly or indirectly, particularlyoily fish and components thereof, and combinations thereof. Other edibleoils are known by those of skill in the art. A wide variety of edibleoils are commercially available from sources known by those of skill inthe art.

The phrase “effective amount” and “in an amount that is effective for”as used herein in connection with one or more vitamins, minerals, edibleoils and/or compositions means an amount of the one or more vitamins,minerals, edible oils and/or compositions that is effective to provide,or enhance, a nutritional, health and/or medical benefit to a mammal,such as a human being. Using the information that is provided herein,and information that is known, those of ordinary skill in the art canreadily determine an amount of one or more vitamins, minerals, edibleoils and/or compositions that would be effective for providing, orenhancing, a nutritional, health and/or medical benefit to a widevariety of mammal under a wide variety of different nutritional, healthor medical situations.

The phrase “essential fatty acids” as used herein means fatty acids thatare necessary for mammals, but that are not synthesized by the body, forexample, linoleic, linolenic and arachidonic acids.

The term “fat” as used herein means any of the various saturated and/orunsaturated (including monounsaturated and polyunsaturated),hydrogenated or unhydrogenated, soft solid, semisolid and/or solidorganic compounds that generally comprise the glyceride esters of fattyacids and associated phosphatides, sterols, alcohols, hydrocarbons,ketones and/or related compounds, and includes components of fats, suchas fatty acids, glycerides and ethyl esters containing fatty acids, orcomponents thereof, and mixtures or other combinations of one or morefats. There is generally no chemical difference between fats and oils,with the only distinction being that fats are generally solid at roomtemperature and oils are generally liquid at room temperature.Components of fats and oils include, but are not limited to, fattyacids, glycerides (mono-, di- and tri-), ethyl and other esters of fattyacids, as well as components thereof and combinations thereof.

The phrase “fatty acids” as used herein means carboxylic acids thatgenerally are derived from, or contained in, an animal, vegetable orother fat or oil, whether saturated, unsaturated, monounsaturated,polyunsaturated, aromatic, essential, nonessential, in a cis or transform, in the ethyl esters, mono-, di- or tri-glycerides, free fattyacids or other forms, and components and combinations of the foregoing.Fatty acids include, but are not limited to, omega-3 fatty acids,omega-6 fatty acids and omega-9 fatty acids, and the specific fattyacids identified below:

FATTY ACIDS Number of Carbon Number of Fat or Oil Common Name AtomsDouble Bonds Source Butyric Acid 4 0 Butterfat Caproic Acid 6 0Butterfat Caprylic Acid 8 0 Coconut Oil Capric Acid 10 0 Coconut OilLauric Acid 12 0 Coconut Oil Myristic Acid 14 0 Palm Kernel Oil PalmiticAcid 16 0 Palm Oil Palmitoleic Acid 16 1 Animal Fats Stearic Acid 18 0Animal Fats Oleic Acid 18 1 Olive Oil Linoleic Acid 18 2 Corn OilAlpha-Linolenic Acid 18 3 Flaxseed (ALA) (Linseed) Oil Gamma-LinolenicAcid 18 3 Borage Oil (GLA) Gadoleic Acid 20 1 Fish Oil Arachidonic Acid(ARA 20 4 Liver Fats, or AA) Peanut Oil, Fish Oil Eicosapentaenoic Acid20 5 Fish Oil (EPA) Behenic Acid 22 0 Rapeseed Oil Erucic Acid 22 1Rapeseed Oil Docosahexaenoic Acid 22 6 Fish Oil (DHA) Lignoceric Acid 240 Most Fats

Other fatty acids are known by those of skill in the art. A wide varietyof fatty acids are commercially available from sources known by those ofskill in the art. Also, edible oils can be separated into theircomponent fatty acids on a capillary column in a gas chromatograph, andthe relative fatty acid contents measured. Additional informationconcerning fatty acids is readily available from the Fatty AcidProducer's Council (New York, N.Y.).

The phrase “fungal oil” as used herein means an oil that is derived orobtained from a fungal source, whether modified or unmodified, such asMucor javanicus, either directly or indirectly. As used herein, thephrase “fungal oil” includes, but is not limited to, one or moreindividual components present in fungal oil, such as DHA, arachidonicacid or other fatty acids. A wide variety of fungal oils arecommercially available from known sources, such as Martek Corp.(Columbia, Md.).

The phrase “hollow oral dosage forms” as used herein means dosage formsfor oral administration, such as hard or soft gelcaps or other capsules,microcapsules or caplets (which include gelatin or some other suitableor conventional material, such materials are known by those of skill inthe art), which have not yet been fully or partially filled with asubstance, material or composition to be enclosed therein (i.e. which donot yet contain all of the substance or composition to be enclosedwithin the oral dosage forms).

The term “hydrogenation” as used herein means a chemical process bywhich hydrogen is added to unsaturated fatty acids to produce partiallyor fully hydrogenated oils. Hydrogenation converts unsaturated bonds inthe oil into saturated bonds. Some of the double bonds may beeliminated, while others may be incompletely transformed. These doublebonds may be transformed from the natural “cis” configuration to the“trans” configuration.

The term “mammal” as used herein means a member of the class Mammalia,and includes, but is not limited to, developing fetuses, human beings(babies, infants, children, adults, pregnant woman, lactating women,women having childbearing potential that are attempting to becomepregnant and the like) and animals.

The phrase “marine oil” as used herein has the meaning described above,and includes, but is not limited to, “fish oil” and one or moreindividual components of marine oil, such as an omega-3 fatty acid,including DHA, EPA, ALA, or a combination thereof. Marine oils include,for example, herring oil, cod oil, anchovy oil, tuna oil, sardine oil,menhaden oil and algae oil. Aquatic lifeforms that are employed toproduce marine oils include, for example, farm-raised or wild,fresh-water or salt-water, fish and shellfish, such as herring, salmon,salmonids, gadoids, shrimp, cod, carp, tilapia, perch, trout, sturgeon,krill, tuna, flat fish, anchovies, sardines, menhaden, shrimp, eels andseals. Marine oils may also be obtained from marine organisms, such ascalanus (Calanus finmarchicus), a 3-4 mm copepod, algae and microalgae,for example, diatoms and dinoflagellates.

The term “medicament” as used herein means a substance or agent thatpromotes a recovery from an injury, illness, disease or disorder (i.e.,that improves the medical condition of the mammal)

The term “minerals” as used herein means minerals that are edible, andincludes those in an elemental, salt or other form. Examples of mineralsinclude, but are not limited to, calcium, copper, fluorine, iodine,iron, magnesium, manganese, molybdenum, potassium, phosphorous, seleniumand zinc, in an elemental form, or in the form of carbonates, oxides,phosphates, silicates, sulfates, sulfides or other forms. Many mineralsare inorganic compounds that are necessary for life and good nutrition,such as calcium, copper, iron, magnesium, potassium and zinc. Additionalinformation about minerals, including an extensive list of minerals, ispresent at the web site http://en.wikipedia.org/wiki/Minerals.

The term “nutrient” as used herein means an agent, substance orcomposition that is preferably soluble in water and insoluble in oil,and that is beneficial to the growth, development and/or health of amammal, or that provides or enhances a nutritional, medical and/or otherhealth benefit to a mammal, and includes, but is not limited to,vitamins, minerals, medicaments and other active agents.

The term “oil” as used herein means a fat that generally is viscous,liquid or liquefiable at room temperature, and includes mixtures andother combinations of one or more oils and/or components of oils, suchas fatty acids, glycerides and/or ethyl esters of fatty acids (orcomponents thereof). Oils may be derived or obtained from animal,marine, algae, fungal, mineral, plant (including vegetables and plantseeds), fruit, nut, synthetic or other sources, and are generallycomposed largely of glycerides of the fatty acids, particularly oleic,palmitic, stearic and linolenic. Oils may be hydrogenated ornon-hydrogenated, and saturated or unsaturated (includingmonounsaturated and polyunsaturated). Plant sources of oil include, butare not limited to, hydrogenated and non-hydrogenated vegetable oils andplant seed oils, Evening Primrose oil, Black Currant seed oil, Borageoil, Borage seed oil, safflower oil, safflower seed oil, sunflower oil,sunflower seed oil, sesame seed oil, peanut oil, olive oil, olive seedoil, corn oil, avocado oil, avocado seed oil, pumpkin seed oil, soy oil,soybean oil, coconut oil, palm oil, palm kernel oil, rapeseed oil,flaxseed (linseed) oil, cotton seed oil, tung oil, oiticica oil andcastor oil. Examples of fats derived from marine sources include fishoil and algae oil. Other oils are known by those of skill in the art. Awide variety of oils are commercially available from sources known bythose of skill in the art.

The phrase “oral dosage forms” as used herein means dosage forms for anoral administration, such as hard or soft gel or other capsules,microcapsules and caplets, and the like. Such oral dosage forms mayinclude in their outer structure gelatin or some other suitable orconventional material. Such materials are known by those of skill in theart.

The phrase “plant seed oil” as used herein means an oil that isextracted or otherwise obtained from a seed of a plant, either directlyor indirectly, particularly oily seeds, including one or more individualcomponents thereof and mixtures thereof. Plant seed oils include, butare not limited to, Black Currant seed oil, Borage seed oil, safflowerseed oil, sunflower seed oil, sesame seed oil, avocado seed oil, pumpkinseed oil, olive seed oil, coconut seed oil, rapeseed oil, flaxseed(linseed) oil, cottonseed oil and tung oil. Other plant seed oils areknown by those of skill in the art.

The phrase “plant oil” as used herein means an oil that is extracted orotherwise obtained from a plant, either directly or indirectly,particularly oily plants, including one or more individual componentsthereof and mixtures thereof. Plant oils include, but are not limitedto, Evening Primrose oil, Borage oil, safflower oil, sunflower oil,peanut oil, walnut oil, almond oil, avocado oil, olive oil, corn oil,soy oil, soybean oil, coconut oil, palm oil, palm kernel oil and castoroil. Other plant oils are known by those of skill in the art.

The term “plurality” as used herein means more than one, such as two,three, four, five, six, seven, eight, nine, ten, fifteen, twenty or thelike.

The phrase “Reference Daily Intakes” (RDIs) as used herein means a labelreference value set by the FDA for use in declaring the nutrient contentof a food on its label or labeling. The FDA has replaced label referencevalues created in 1973 that are known as “U.S. Recommended DailyAllowances” (U.S. RDAs) with RDIs.

The phrases “solid-state” and “solid-state form” as used herein meanhaving a form that is a soft solid, a semisolid or a solid (i.e. notliquid) including size-reduced solids, for example, powders, granulesand milled materials. Methods are known by those of skill in the art forsize reducing solid particles, such as milling, grinding, cutting andlike methods.

The phrase “suspending agent” as used herein means a substance, materialor composition that is edible, and that has an ability to initiate,permit, promote, enhance or maintain a suspension of one or moresoft-solid, semi-solid or solid components in a semi-liquid or liquidvehicle. Examples of suspending agents include, for example, lecithin,and yellow beeswax.

The term “suspension” as used herein means an incorporation of one ormore solid-state components into a semi-liquid or liquid vehicle, andincludes colloidal and other types of suspensions. Preferably, thesuspension is a uniform suspension (i.e. the components are uniformlypresent in a semi-liquid or liquid vehicle). If the particle sizes ofthe component particles are larger than colloidal dimensions (i.e., theyare not small enough to pass through filter membranes), the componentparticles may have a tendency to precipitate (if they are heavier thanthe suspending medium) or agglomerate and rise to the surface (if theyare lighter than the suspending medium). In both cases, the componentparticles may “settle out” of the suspension.

The phrase “temporarily suspended” as used herein in connection with oneor more water soluble vitamins and/or minerals and one or more edibleoils means that the one or more water soluble vitamins and/or mineralsare partially or fully, and preferably fully, suspended in the one ormore edible oils for a period of time that is sufficient to permit theone or more water soluble vitamins and/or minerals and the one or moreedible oils preferably to be uniformly inserted into two or more holloworal dosage forms, such as hollow gel capsules, gelcaps, or caplets(i.e., in a manner that the same or similar amount of the one or morevitamins, minerals and/or edible oils becomes inserted into the two ormore hollow oral dosage forms). Such a period of time may vary dependingupon a wide variety of factors, such as the numbers and types of thewater-soluble vitamins and/or minerals and edible oils being employed,the number of hollow oral dosage forms being filled and the like, andcan readily be determined by those of skill in the art.

The phrase “uniformly inserted into” when used herein in connection withone or more water-soluble vitamins and/or minerals, one or more edibleoils and hollow oral dosage forms means that approximately the samequantities of the one or more water-soluble vitamins and/or minerals andthe one or more edible oils are generally placed into each of the holloworal dosage forms being filled (whether they are being partially orcompletely filled). For example, if one hundred hollow soft gelcapsules, gelcaps, or caplets are being filled with one or more edibleoils having one or more water-soluble vitamins and/or minerals suspendedtherein, approximately the same quantities of the one or morewater-soluble vitamins and/or minerals and the one or more edible oilswill generally be present in each of the soft gel capsules, gelcaps, orcaplets after the filling operation.

The phrase “unit dosage form” as used herein means one individual dosageform for an oral administration to a mammal, such as one hard gelcapsule containing a composition of the invention.

The term “vitamin B6” means know chemical forms of vitamin B6 including,but not limited to pyridoxine, pyridoxamine, and pyridoxal.

The term “vitamin B9” means folic acid folate or one or more naturalisomers of reduced folate, including but not limited to L-methylfolate,L-5-methyl-tetrahydrofolate, L-5-methyl-tetrahydrofolic acid,(6S)-tetrahydrofolic acid, (6S)-5-methyl-tetrahydrofolic acid,5-methyl-(6S)-tetrahydrofolic acid, 5-formyl-(6S)-tetrahydrofolic acid,10-formyl-(6R)-tetrahydrofolic acid, 5,10-methylene-(6R)-tetrahydrofolicacid, 5,10-methenyl-(6R)-tetrahydrofolic acid,5-formimino-(6S)-tetrahydrofolic acid, (6S)-5-methyl-tetrahydrofolicacid and polyglutamyl derivatives of tetrahydrofolate acid.

The term “vitamin B12” means known chemical forms of vitamin B12including, but not limited to cyanocobalamin, cobalamin, and reducedforms of cobalamin, and also includes all forms both bound and unboundto recombinant intrinsic factor.

The phrase “without being degraded” as used herein in connection withwater-soluble vitamins, minerals and/or edible oils means that nodegradation, or substantially no degradation, preferably occurs. Whensubstantially no degradation occurs, some minimal degradation may stilloccur, but the amount of such degradation is generally insufficient toprevent or reduce the nutritional, medical or other health benefitsprovided by the nutrient or edible oil to the mammal.

The phrase “water-soluble” as used herein in connection withwater-soluble vitamins and/or minerals means that the vitamins and/orminerals dissolve partially or fully (and preferably fully) in water,and preferably form an equilibrium concentration of at least about 0.001mg/mL at 25° C.

Edible Oils

Any one or more of a wide variety of edible oils, or combinationsthereof, may be employed in the compositions of the invention,including, but not limited to, those specifically discussed herein.Because of the nutritional, medical and/or other health benefits thatthey can provide to mammals, edible oils that are preferred for use inthe compositions of the invention are those that are, or are rich in(contain large quantities of), essential fatty acids, omega-3 fattyacids, omega-6 fatty acids and/or omega-9 fatty acids, particularly DHA,EPA, ARA, AA, ALA or GLA, ocosapentaenoic acid, eicosatetraenoic acid,moroctic acid, heneicosapentenoic acid, gamma-linolenic acid, linoleicacid, arachidonic acid and oleic acid. As a result of an enhancedstability, such such fatty acids are preferably present in their ethylesters or tryglycerides forms. The most preferred edible oils for use inthe compositions, of the invention are those that are, or are rich in,omega-3 fatty acids and/or essential fatty acids, such as DHA.

The edible oils that may be employed in the compositions of theinvention are commercially available from sources known by those ofskill in the art. Sources for these edible fats and oils include, forexample, Martek Corp. (Columbia, Md.), Ocean Nutrition Canada, Ltd.(Bedford, Nova Scotia, Canada), DSM (Heerlen, NL), Pronova Biocare AS(Lysakar, Norway), Napro AS (Brattvaag, Norway), Berg Lipotech AS(Norway), ADM Food Oils (Decatur, Ill.), and Oilseeds International,Ltd. (San Francisco, Calif.).

Edible oils, such as omega-3 marine oils, are generally commerciallyavailable in the ethyl esters, triglycerides or free fatty acids forms.The ethyl esters form of edible oils result from breaking apart theoriginal triglyceride molecules through the known process of“ethylation,” which is performed to increase or concentrate the level ofomega-3 fatty acids, while removing the less desirable fatty acids.Ethyl esters of EPA and DHA are available from DSM (Heerlen, NL) underthe name Ropufa® 75 n-3 EE, and from other oil suppliers describedherein.

The triglycerides form of edible oils generally consists either of anunconcentrated fish oil (about 18% EPA and about 12% DHA), or of aconcentrated fish oil that has been reconverted (re-esterified) back tothe tri-glycerides form. In the processing of marine and other edibleoils, the objective is generally to remove existing free fatty acids,monoglycerides and diglycerides to form more stable compositions of thefatty acids, which is the triglycerides or ethyl esters forms of thefatty acids.

The fatty acids form of edible oils generally results fromsaponification and neutralization of the triglycerides, using knowntechniques, whereby the glycerol backbone of the triglycerides isgenerally severed, leaving only the free fatty acid form. Suchprocessing techniques preferably result in the edible oils having anacid value below about 5.0 mg KOH/g and unsaponified matter below about1.5% w/w.

Methods are also known by those of skill in the art for extracting oilfrom fish. For example, raw fish can be placed into a cooker and heatedto a temperature of about 95°. This temperature can be reached byheating the fish meat directly, or indirectly, with steam. Such heatingaids in the coagulation of proteins in the fish meat. As the proteinscoagulate, the heating also helps recover fat and water from the fishmeat. The cooked fish meat can be collected and conveyed to screwpresses, which aid in the removal of any remaining oil and/or water fromthe fish. The resulting liquid, which is called “pressliquor,” undergoesa series of known decanting and separating techniques. Decanters areemployed to separate solid fish meat from the liquid. The pressliquorcan be pumped into cylindrical bowls and conveyers to rotate. Therotation of the decanter helps to force the solids to the outside of thebowl, where they are collected. The remaining liquid continues throughthe process. After decanting, the pressliquor can be pumped through aseparator. A high-speed rotation of separator plates results in theseparation of the oil from the water, resulting in a fish oil. Marineoil can be extracted from aquatic lifeforms other than fish in a similarmanner. All of the equipment and techniques employed in extractingmarine oil from fish and other aquatic lifeforms are known and/orcommercially available.

Methods are also known by those of skill in the art for extracting oilfrom seeds, including the known solvent extraction and mechanicalextraction (cold processing) methods.

Oils that are extracted from fish, plants and other sources may have apronounced color, flavor and aroma. If the refining of such oils doesnot cause the amount of water-soluble vitamins and/or minerals presenttherein to be reduced or eliminated, it is, thus, preferable that edibleoils that are employed in the compositions of the invention, and thatare extracted from such sources, be refined, deodorized andsubstantially free of fish meat, flesh, seeds or other solids. Suchrefinement methods are known by those of skill in the art, and generallyresult in a clean, “finished” oil product. When some oils, such asEvening Primrose oil, are refined, however, water-soluble vitamins orminerals present in the oils are significantly reduced by the refinementprocess. Those of skill in the art know which edible oils have theirwater-soluble vitamins or minerals reduced by refinement processes.Unrefined oils are sometimes referred to as “virgin” or “extra virgin”oils.

Marine (and other) oils employed in the methods of the invention maypreferably be refined and deodorized using methods known in the art. Forexample, methods for processing marine and other edible fats and oilsare described in “Fish Oils: Their Chemistry, Technology, Stability,Nutritional Properties and Uses” (The Avi Publishing Company, Inc.,1967); Marschner et al. U.S. Pat. No. 4,804,555, entitled “SimultaneousDeodorization and Cholesterol Reduction of Fats and Oils;” and A. P.Bimbo, “Production of Fish Oil,” Fish Oils in Nutrition, Chapter 6,141-180 (M. E. Stansby ed., New York, Van Nostrand Reinhold); thedisclosures of which are expressly incorporated by reference herein.

Both physical refining and chemical refining can generally be employedto refine oils that can be employed in compositions for oraladministration. Physical methods include the known filtering,deodorizing and winterization processes. Chemical methods include theknown degumming, neutralization and bleaching processes. Additionalinformation concerning the refinement of oils for use in compositionsfor oral administration is present at the web sitewww.sanmarkltd.com/processing.htm.

Marine oil purification is a process in which crude oils are refined toremove fish meat and flesh, as well as other substances that maycontribute to off flavor, off odor, undesirable color or keepingquality. The oils can be purified, or fatty acids can be removed fromthe oils, by degumming the oils (by washing the oils generally usingwater, salts and acids in order to remove waxes, phosphates and otherimpurities therefrom). After the impurities are removed from the oilsthrough degumming, the oils can undergo a neutralization process. Alkalican be mixed with the oils to remove free fatty acids, which cancontribute to rancidity. A resulting soap/oil mixture can be heated to,for example, 180° F., and pumped through a separator that removes thesoap from the oil.

After the above “chemical” refinements have been made, the oils can besubjected to “physical” refinements. The first of these physicalrefinements is generally the removal of odor compounds from the oils.This can be accomplished by applying a vacuum steam distillation processto the oils. Steam distillation can be followed by winterization, whichinvolves a cooling of the oils. As a result of this cooling process,some oils become crystallized, and can thereafter be removed from otheroils using filtration techniques. This results in the oils being moreuniform. After winterization, the oils can be bleached and hydrogenised,which processes can stabilize the oils. Bleaching involves the use ofclay to remove color and impurities from the oils. The oils can bebleached by heating, for example, to about 130° F., and mixing them withclay. The mixture can be held for several minutes, and then the hot oilcan be filtered from the clay and cooled. Hydrogenation can becompleted, following bleaching, by pumping pressurized hydrogen into anagitated tank filled with the oils. This is generally done in thepresence of a catalyst metal, such as nickel. Hydrogenation can beperformed at a temperature, for example, of about 204° C., and apressure of, for example, 60 psig.

Similar known methods to those described above can be employed withother types of edible oils. Further, other methods known by those ofskill in the art can also be employed to purify marine and other typesof edible oils, or to remove fatty acids from such oils. Methods forprocessing marine and other edible fats and oils are well known in theart. (See, for example, “Fish Oils: Their Chemistry, Technology,Stability, Nutritional Properties and Uses” (The Avi Publishing Company,Inc., 1967); Marschner et al. U.S. Pat. No. 4,804,555, entitled“Simultaneous Deodorization and Cholesterol Reduction of Fats and Oils;”A. P. Bimbo, “Production of Fish Oil,” Fish Oils in Nutrition, Chapter6,141-180 Stansby ed., New York, Van Nostrand Reinhold).

In order to permit edible oils employed in the compositions of theinvention to provide maximum nutritional, health and/or medicalbenefits, it is preferred that the edible fats and oils not behydrogenated. As discussed hereinabove, the hydrogenation of marine orother edible oils by decreasing polyunsaturation, including n-3 fattyacid components, generally correspondingly decreases the health value ofsuch oils.

In the United States, there are currently no Reference Daily Intakes(RDIs), Daily Reference Values (DRVs) or Daily Values (DVs) foressential fatty acids or other edible oils. However, the World HealthOrganization recommends that pregnant and lactating women consume 5% oftheir daily caloric intake as essential fatty acids. It is recommendedthat healthy adults consume 4% to 10% of their daily caloric intake asessential fatty acids.

The amount of one or more edible oils that may be included in thecompositions of the invention is an amount that is preferably effectivefor providing or enhancing some nutritional, health, medical or otherbenefit to the mammal, and that is not harmful to the mammal.

DHA may, for example, optionally be included as a component of thecompositions of the invention in an amount that is effective forproviding, or increasing the supply of DHA to developing fetuses orbabies through, for example, placentas or breast milk, or to othermammals, and that is not harmful to developing fetuses or breast-feedingbabies, or to other mammals. The amount of DHA that is preferablypresent in these compositions ranges from about 0.05 to about 3 weightpercent of the total weight of the compositions, and more preferablyranges from about 0.2 to about 0.4 weight percent, with about 0.3 weightpercent being most preferred (for pregnant women, lactating women, andwomen having childbearing potential that are attempting to becomepregnant, or for other mammals).

Edible oils are susceptible to oxidation, degradation and decomposition,particularly when they are exposed to oxygen (present in the air orotherwise), or when they are in contact with substances that initiate orcatalyze (accelerate the rate of) the oxidation, degradation and/orother decomposition of edible oils, such as free radicals or certainminerals. Free radicals are highly reactive molecular fragments thathave one or more unpaired electrons and generally act as initiators orintermediates in oxidation reactions. Minerals, particularly copper,iron, magnesium, manganese, molybdenum and zinc, generally catalyze anoxidation and/or degradation of edible oils. Those of skill in the artknow which vitamins, minerals and other water-soluble vitamins initiateor catalyze the oxidation, degradation and/or other decomposition ofedible oils. It is, thus, preferred that the compositions of theinvention comprise vitamins, minerals and other water-soluble vitaminsand/or minerals that do not initiate or catalyze an oxidation,degradation or other decomposition of edible oils.

The amount of oxidation, degradation and decomposition that occurs to anedible oil, or to a composition containing one or more edible oils, canbe determined by tests known by those of skill in the art. The mostcommonly used measure for testing an oxidation of an edible fat or oil,or of a solid or liquid food product containing one or more edible fatsor oils, is the Peroxide Value Test, which measures the concentration ofthe immediate products of oxidation (peroxides). However, these initialperoxide products are themselves degraded over time to variousaldehydes, and these aldehyde secondary products are not detected by thePeroxide Value Test. A second known test, the Anisidine Test, may beused to detect the secondary products. Thus, the Peroxide Value Testmeasures the degree to which oxidation is taking place at the presentmoment, and the Anisidine Test measures the amount of historicaloxidation over the life of a edible fat, oil or food product. These twomeasures may be combined to give a total oxidation (or TOTOX) value,which is calculated as:

TOTOX=Anisidine Value+(2×Peroxide Value).

Known organoleptic testing procedures can also be employed to test thetaste and smell of edible fats and oil, and food products containing oneor more edible fats and/or oils.

Edible oils include vegetable-based oils, such as soybean, corn,cottonseed, peanut, safflower, sunflower, canola and olive oil. Inaddition, edible oils include marine oils (including “fish oils”), suchas those that are obtained from aquatic lifeforms, either directly orindirectly, particularly oily fish. Marine oils generally contain highlevels of omega-3 fatty acids. Marine oils having a total omega-3 fattyacid content of greater than about 5 weight percent include thosederived from menhaden oil, herring, capelin, anchovy, cod liver, salmonoil, sardine oil and mixtures thereof.

As those of skill in the art will appreciate, any one or more of a widevariety of edible fats and/or oils, and preferably those that containomega-3 fatty acids, including DHA and/or EPA, may be employed in thecompositions and methods of the present invention, including, but notlimited to, the marine oils, fungal oils, plant oils and plant seed oilsand combinations thereof. Edible fats and oils that are preferred foruse in the methods of the invention are those that are rich in omega-3fatty acids, such as DHA. The most preferred edible fats and oils foruse in the methods of the invention are those containing at least about5 percent by weight DHA, more preferably from about 10 percent by weightDHA to about 80 percent by weight DHA and most preferably about 20percent by weight DHA to about 70 percent by weight DHA. DHA may beindependently isolated and added to an omega-3 oil, or an omega-3 oilmay be otherwise enriched in DHA content as is known in the art. Omega-3oils additionally or alternatively may contain amounts of other omega-3fatty acids, such as EPA.

Vitamins and Minerals

A wide variety of oil and/or water-soluble vitamins, minerals, andcombinations thereof, may be used in the methods and compositions of theinvention in varying quantities.

A primary aspect of the invention is that water soluble vitamins and/orminaerals will be present in the compositions. However, it is alsocontemplated that soluble vitamins and minerals can be present inaddition to the, or alternatively to, water soluble vitamins and/orminerals. The oil soluble vitamins and/or minerals can be dissolved inone or more edible oils or be present in its own phase or mixturesthereof. Oil soluble vitamins and/or minerals can, optionally, be addedto one or more other edible oils or may be naturally occurring in one ormore edible oils.

Water soluble vitamins and minerals that can be used in the methods andcompositions of the invention include, but are not limited to, VitaminB1 (as Thiamin or Thiamine Mononitrate), Vitamin B2 (as Riboflavin),Vitamin B3 (as Niacin), Vitamin B₆ (as Pyridoxine or PyridoxineHydrochloride), Vitamin B9/M (Folic Acid or Folate) or of reducedFolate, including but not limited to L-methylfolate,L-5-methyltetrahydrofolate, L-5-methyl-tetrahydrofolic acid,(6S)-tetrahydrofolic acid, (6S)-5-methyl-tetrahydrofolic acid,5-methyl-(6S)-tetrahydrofolic acid, 5-formyl-(6S)-tetrahydrofolic acid,10-formyl-(6R)-tetrahydrofolic acid, 5,10-methylene-(6R)-tetrahydrofolicacid, 5,10-methenyl-(6R)-tetrahydrofolic acid,5-formimino-(6S)-tetrahydrofolic acid, and polyglutamyl derivatives oftetrahydrofolate acid, Vitamin B12 (cyanocobalamin, cobalamin, andreduced forms of cobalamin), Biotin, Vitamin C (Ascorbic Acid), Folacin,Niacinamide, Calcium (as Calcium Carbonate), Iron (as Ferrous Fumarate),Phosphorus, Pantothenic Acid (as Calcium Pantothenate), Iodine (asPotassium Iodide), Magnesium (as Magnesium Oxide), Zinc (as Zinc Oxide),Selenium (as Sodium Selenate), Copper (as Cupric Oxide), Manganese (asManganese Sulfate), Chromium (as Chromium Chloride), Molybdenum (asSodium Molybdate), Choline, Fluoride, Chloride, Potassiuin, Sodium,Biotin and various mixtures or other combinations thereof.L-methylfolate, or Metafolin™ (Merck-Eprova AG Schaffhausen,Switzerland), may also be used in place of or in addition to folic acidor folate. Recombinant Intrinsic Factor (rhIF) with bound Cobalamin(Cobento Biotech A/A, Science Park, Aarhus, Denmark) may be used inplace of or in addition to vitamin B12.

Recombinante Intrinsic Factor is thought to he vital for the transportof vitamin B12 within the body. Intrinsic factor is normally present inthe stomach. More specifically it is a glycoprotein secreted by parietal(humans) cells of the gastric mucosa. In humans, it has an importantrole in the absorption of vitamin B12 in the intestine.

Oil soluble vitamins and minerals that may be employed in the methodsand compositions of the invention include, but are not limited to,Vitamin A, Vitamin D, Vitamin E (as dl-Alpha Acetate or d-alpha Nat'l),Vitamin K and Tocopherol.

Compositions of the invention may be formulated using anypharmaceutically-acceptable forms of the vitamins and/or mineralsdescribed above, including their salts, which are known by those ofskill in the art. For example, useful pharmaceutically-acceptablecalcium compounds include any of the well-known calcium supplements,such as Calcium Carbonate, Calcium Sulfate, Calcium Oxide, CalciumHydroxide, Calcium Apatite, Calcium Citrate-Malate, Bone Meal, OysterShell, Calcium Gluconate, Calcium Lactate, Calcium Phosphate, CalciumLevulinate, and the like. Pharmaceutically-acceptable magnesiumcompounds include Magnesium Stearate, Magnesium Carbonate, MagnesiumOxide, Magnesium Hydroxide and Magnesium Sulfate.Pharmaceutically-acceptable iron compounds include any of the well-knownIron II (ferrous) or Iron III (ferric) supplements, such as FerrousSulfate, Ferric Chloride; Ferrous Gluconate, Ferrous Lactate, FerrousTartrate, Iron-Sugar-Carboxylate complexes, Ferrous Fumarate, FerrousSuccinate, Ferrous Glutamate, Ferrous Citrate, Ferrous Pyrophosphate,Ferrous Cholinisocitrate, Ferrous Carbonate, and the like. The vitaminsand/or minerals that may be included in compositions of the inventionmay be microencapsulated in a coating of fat, microcrystalline celluloseor similar material in order to prevent their degradation under variousconditions.

The vitamins and/or minerals that are preferred for use in the methodsand compositions of the invention are those that have Daily Values(DVs), Reference Daily Intakes (RDIs) and/or Daily Reference Values(DRVs) described by the U.S. Food and Drug Administration (FDA) in itsregulations or publications, such as the Code of Federal Regulations orFederal Register, Vol. 58, No. 3 (1993), for the following fivecategories of persons: (1) infants (persons not more than 12 months ofage); (2) children under 4 years of age (persons 13 through 47 months ofage); (3) adults and children that are 4 or more years of age; (4)pregnant women; and (5) lactating women. The most preferred vitaminsand/or minerals for use in the methods and compositions of the inventionare vitamin B6, vitamin B9 and vitamin B12.

One or more vitamins and/or minerals may be employed in the compositionsof the invention in any quantity that is effective for providing, orenhancing, a nutritional, medical and/or other health benefit to aparticular mammal, and that is safe for consumption by the particularmammal, such as pregnant women, lactating women or women havingchildbearing potential that are attempting to become pregnant or theirdeveloping fetuses or babies (ie., a quantity that would not cause harmto a woman consuming the composition, or to her developing fetus orbreast-feeding baby). This quantity may vary depending upon theparticular vitamins and/or minerals chosen for use, the age, size,weight and health condition of the mammal and like considerations, butgenerally ranges from about 2.5 to about 50 weight percent of the totalweight of the compositions, and more preferably ranges from about 5 toabout 25 weight percent, with about 10 weight percent being mostpreferred. The DVs described by the FDA, for example, in FederalRegister, Vol. 58, No. 3 (1993) or in 21 CFR 101.9, for the differentcategories of human beings described above may be employed to determinesuch quantity for different mammals, and are set forth below.

DAILY VALUES Persons Children that are 4 Under 4 Pregnant LactatingYears or Units Infants Years Women Women Older Vitamins Vitamin A IU1,500 2,500 8,000 8,000 5,000 Vitamin C mg 35 40 60 60 60 Vitamin D IU400 400 400 400 400 Vitamin E IU 5 10 30 30 30 Vitamin K μg *** *** ****** 80 Vitamin B1 mg 0.5 0.7 2.5 2.5 1.5 Vitamin B2 mg 0.6 0.8 2.0 2.01.7 Vitamin B3 mg 8. 9 20 20 20 Vitamin B6 mg 0.4 0.7 2.5 2.5 2.0Vitamin B9 mg 1 0.2 0.8 0.8 ** Folate * mg *** *** *** *** 0.4 VitaminB12 μg 2 3 8 8 6 Biotin mg 0.05 15 0.3 0.3 0.3 Minerals Pantothenic Acidmg 3 5 10 10 10 Calcium g 0.6 0.8 1.3 1.3 1 Phosphorus g 0.5 0.8 1.3 1.31 Iodine μg 45 70 150 150 150 Iron mg 15 10 18 18 18 Magnesium mg 70 200450 450 400 Copper mg 0.6 1.0 2.0 2.0 2.0 Zinc mg 5 8 15 15 15 Seleniumμg *** *** *** *** 70 Manganese mg *** *** *** *** 2.0 Chromium μg ****** *** *** 120 Molybdenum μg *** *** *** *** 75 Chloride mg *** *** ****** 3,400 * Folate is the anion form of folic acid (currently known asfolacin or Vitamin B9 and formerly known as vitamin M). Vitamin B9 canbe present as folic acid or one or more natural isomers of reducedFolate, including but not limited to L-methylfolate,L-5-methyltetrahydrofolate, L-5-methyl-tetrahydrofolic acid,(6S)-tetrahydrofolic acid, (6S)-5-methyl-tetrahydrofolic acid,5-methyl-(6S)-tetrahydrofolic acid, 5-formyl-(6S)-tetrahydrofolic acid,10-formyl-(6R)-tetrahydrofolic acid, 5,10-methylene-(6R)-tetrahydrofolicacid, 5,10-methenyl-(6R)-tetrahydrofolic acid,5-formimino-(6S)-tetrahydrofolic acid, (6S)-5-methyltetrahydrofolic acidand polyglutamyl derivatives of tetrahydrofolate. ** Information notpresent in 21 CFR 101.9. *** Information not present in FederalRegister, Vol. 58, No. 3 (1993).Additional information is available at www.nal.usda.gov.

It is important that the quantity of each vitamin and/or mineral used ina method or composition of the invention be safe for consumption bypregnant women, lactating women or women having childbearing potentialthat are attempting to become pregnant, and is safe for their developingfetuses or babies, or is safe for consumption by other mammals thatconsume the composition. Larger quantities of certain vitamins and/orminerals may cause damage to a developing fetus or baby, or to othermammals. Those of skill in the art know the quantities of vitamins andminerals above the U.S. DVs for pregnant women, lactating women or womenhaving childbearing potential that are attempting to become pregnant, orfor other mammals, that would be harmful for the mammal consuming thecomposition, or for their developing fetuses or babies.

Set forth hereinbelow are the approximate preferred ranges of the dailyquantities of the various vitamins and minerals that may generally beused in one composition of the invention (or divided between more thanone composition of the invention for consumption during a one-dayperiod) for mammals, including pregnant women, lactating women or womenhaving childbearing potential that are attempting to become pregnant(from about one quantity to about another quantity), as well as morepreferred ranges, and the most preferred quantities for pregnant andlactating women.

PREFERRED RANGES Most More Preferred Quantity Pre- Most Quantity for forferred Preferred Pregnant Lactating Vitamin Units Range Range WomenWomen Vitamin A IU 0-9,000 1,500-8,000 8,000 8,000 Vitamin C mg 0-1,000 35-500 60 60 Vitamin D IU 0-800 200-400 400 400 Vitamin E IU 0-1,500 5-400 30 30 Vitamin K μg 0-80 10-80 10 10 Vitamin B1 mg 0-50 0.5-10 2.5 2.5 Vitamin B2 mg 0-50 0.5-25  2.0 2.0 Vitamin B3 mg 0-60  5-40 2020 Vitamin B6 mg 0-50 0.4-30  2.5 2.5 Vitamin B9 mg 0-2 0.2-1.0 0.8 0.8Vitamin B12 μg 0-1,000 2.0-18  8 8 Biotin mg 0-15 0.05-15   0.3 0.3Mineral Pantothenic mg 0-20  3-15 10 10 Acid Calcium g 0-3 0.2-2.0 1.31.3 Phosphorus g 0-2 0.1-1.5 1.3 1.3 Iodine μg 0-200  45-150 150 150Iron mg 0-100  5-50 18 18 Magnesium mg 0-600  50-500 450 450 Copper mg0-2 0.1-2   2 2 Zinc mg 0-30  1-25 15 15 Selenium μg 0-400  60-100 60 70Manganese mg 0-5 0.1-5   5 5 Chromium μg 0-150  0.1-120 25 25 Molybdenumμg 0-75 20-75 25 25 Chloride mg 0-3,400 2,000-3,400 Not Not EstablishedEstablished Choline mg 0-1,000 300-600 450 550 Fluoride mg 0-5 1-4 NotNot Established Established Potassium mg 0-80 10-80 Not Not EstablishedEstablished Sodium mg 0-2,400   10-1,000 Not Not Established Established

One composition of the invention may contain one or more of the above(or other) vitamins and/or minerals in their preferred or other quantityrange (or in their more preferred range, or in the most preferredquantity for pregnant women, lactating women or women havingchildbearing potential that are attempting to become pregnant, or forother mammals). Alternatively, one composition may contain each of thesevitamins and/or minerals m one half, one third, one forth, one fifth,one sixth, and so forth, of these quantities. Varying combinations of awide variety of vitamins and minerals may also be employed.

The compositions of the invention may contain any number, and anycombination, of edible oils, such as essential and non-essential fattyacids. In a preferred embodiment of the invention, only one edible oilis present in the compositions, and the edible oil comprises abeneficial fatty acid, preferably an omega-3 fatty acid, such asdocosahexanoic acid (DHA). In this embodiment, the DHA content is about45 to 70 weight percent. The DHA content of the compositions of theinvention is preferably greater than about 5 weight percent of the totalweight of the edible oils, and more preferably, greater than about 10weight percent of the total weight of the edible oils, and still morepreferably greater than about 25 weight percent of the total weight ofthe edible oils, such as a DHA content of about 50 weight percent of thetotal weight of the edible oils, or greater.

Vitamins and minerals are commercially available from sources known bythose of skill in the art, such as Hoffmann-LaRoche Inc. (Nutley, N.J.).Additionally, vitamin A can be derived from dark green, dark yellow andorange vegetables, such as carrots and sweet potatoes and coloredfruits, such as peaches, oranges, and apple. Vitamin B1 may be derivedfrom wheat germ, nutritional yeast, cooked beans and peas, collardgreens, raisins, oranges, nuts, and whole grains. Vitamin B2 may bederived from dark green leafy vegetables, avocado, wheat germ, and wholegrains. Vitamin B3 (Niacin) may be derived from cooked dried beans andpeas, nuts, whole wheat and grains, potato, and nutritional yeast.Vitamin B6 (Pyridoxine) may be derived from cooked dried beans and peas,nutritional yeast, wheat germ, nuts, bananas, avocados, leafy greens,cabbage, cauliflower, potatoes, whole grains, and dried fruit. VitaminB7(Biotin) may be derived from oatmeal, nutritional yeast, legumes,soybeans, mushrooms, bananas, nuts, and whole grains. Vitamin B12(cyanocobalamin, cobalamin, and/or reduced forms of cobalamin) may bederived from nutritional yeast, fortified foods and beverages such ascereals, soymilk and orange juice. Folate (Folic Acid) may be derivedfrom dark green leafy vegetables, nutritional yeast, beans, avocados,wheat germ, various fruits like banana, orange, and whole grains.Pantothenic Acid may be derived from legumes, soybeans, avocados,mushrooms, green vegetables, bananas, oranges, whole grains and wheatgerm. Vitamin C (Ascorbic Acid) may be derived from fresh fruits andvegetables, green pepper, broccoli, citrus fruits, tomatoes, guava andstrawberries. Vitamin D may be derived from sunlight, fortified foodsand beverages. Vitamin E (Tocopherol) may be derived from vegetableoils, seeds, nuts, wheat germ, spinach, peaches, avocados, broccoli,dried prunes and whole wheat. Vitamin K may be derived from green orleafy vegetables, broccoli, turnip greens, cabbage, cauliflowers andavocados.

Although a wide variety of vitamins and/or minerals may be employed inthe methods and compositions of the invention, compositions of theinvention preferably include vitamin B6, vitamin B9 and/or vitamin B12.Vitamin B6 (as Pyridoxine or Pyridoxine Hydrochloride) may, for example,be present in the composition in an amount that preferably ensures thepresence of from at least about 1 mg to about 50 mg per unit dosageform. Vitamin B9/M (Folic Acid) may, for example, be present in thecomposition in an amount that preferably ensures the presence of from atleast about 100 μg to about 1000 μg per unit dosage form. Vitamin B12(cyanocobalamin, cobalamin, and/or reduced forms of cobalamin) may, forexample, be present in an amount that preferably ensures the presence offrom at least 200 μg to about 2000 μg per units dosage form. A varietyof vitamins and minerals, including vitamin B6, vitamin B9 and vitaminB12 are commercially available from sources known by those of skill inthe art, such as Hoffmann-LaRoche Inc. (Nutley, N.J.). Preferably,solid-state vitamins are provided as finely divided powders, such asamorphous powders or very finely milled crystalline powders. Thisgenerally ensures content uniformity and inhibits agglomeration of thevitamins and/or minerals in the compositions of the invention.

In addition to vitamins, minerals and edible oils, the compositions ofthe invention may contain one or more additional pharmaceuticallyacceptable compounds, drugs, substances, ingredients or materials.

Wetting agents, emulsifiers, lubricants, coloring agents, releaseagents, coating agents, sweetening agents, flavoring agents,preservatives, suspending agents, antioxidant agents, additionalcarriers and other suitable agents may also, optionally, be includedwithin the compositions of the invention. However, such materials shouldbe compatible with other ingredients that are present in thecompositions, and not harmful to mammals.

Pharmaceutically acceptable antioxidants that may, optionally, beincluded in the compositions of the invention include, for example: (a)water soluble antioxidants, such as ascorbic acid, cysteinehydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfiteand the like; (b) oil-soluble antioxidants, such as ascorbyl palmitate,butylated hydroxytoluene (BHT), lecithin, propyl gallate,alpha-tocopherol and the like; and (c) metal chelating agents, such ascitric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaricacid, phosphoric acid and the like.

Pharmaceutically acceptable suspending agents that may, optionally, beincluded in the compositions of the invention include, for example,ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitanesters, microcrystalline cellulose and mixtures thereof.

Unit Dosage Forms of Compositions

A unit dosage form of the compositions of the invention will typicallycomprise a soft or hard gel capsule, gelcap, caplet or other oral dosageform containing a combined amount from about 0.25 ml to about 5 ml ofone or more edible oils, and an effective amount of one or more vitaminsand/or minerals, which are preferably water soluble, as is describedherein. The unit dosage may, optionally, also contain one or moreantioxidant agents, suspending agents, and/or emulsification agents aspractically needed, or as desired, in quantities that are beneficial,which quantities may readily be determined by those of ordinary skill inthe art.

A preferred unit dose of a composition of the invention contains acombined amount of about 700 mg of oils, of which 500 mg is preferablyomega-3 oil including 350 mg of DHA and 35 mg EPA. Each unit dose of theone or more edible composition also preferably comprises about 12.5 mgof vitamin B6, about 500 μg of vitamin B12 and about 1000 mg of folicacid (vitamin B9), as well as a trace amount of tocopherol (anantioxidant), as is known in the art. Yellow beeswax and/or lecithin arealso preferably included in the compositions of the invention, and arepreferably added to the one or more edible oils to act as suspendingagents so that the vitamins and/or minerals do not settle during theirwait in a hopper for encapsulation. In this unit dose, it is preferredto administer two gel capsules (or other unit dosage form) each day(either two gel capsules together once per day or spaced apart in anydesire time interval, such as 1, 2, 3, 4, 5, 6, 7 or 8 hours during theday.

Method of Production

The compositions of the invention may be produced by admixing orotherwise combining the above-described ingredients to form asuspension, or other desired form, of the one or more vitamins and/orminerals in the one or more edible oils using, for example, methods andequipment known by those of skill in the art, followed by an injectionor other insertion of the resulting mixture (suspension, emulsion or thelike) into hollow oral dosage forms, such as empty gelatin capsules,gelcaps or caplets.

Because, in some cases, some or all of the one or more vitamins and/orminerals may settle out from a suspension, emulsion or other form aftera short period of time, the composition is preferably mixed one or moretimes, using known or other mixing, circulating, stirring or shakingtechniques, prior to inserting the composition into the hollow gelatincapsules or other oral dosage forms. Such mixing, which should permitthe composition to be uniformly inserted into two or more of the holloworal dosage forms, is preferably performed immediately prior to suchinsertion. However, the mixing can be performed at any time prior tosuch insertion that is effective for permitting the composition to beuniformly inserted into two or more of the hollow oral dosage forms.This period of time, and the number of times that the composition shouldbe mixed, may vary depending upon a wide variety of circumstances, suchas the number of oral dosage forms being filled and the number andquantities of water-soluble or other vitamins and/or minerals and edibleoils that are present in the composition, or whether suspending agentsare utilized and may readily be determined by those of skill in the art.Once the composition is inserted into or encapsulated within, the holloworal dosage form, it generally is no longer necessary to have the one ormore water-soluble or other vitamins and/or minerals suspended, orotherwise distributed, within the one or more edible oils. A mammal thatconsumes one or more filled gelatin capsules (or other oral dosageforms) should receive approximately the same amount of water-soluble orother vitamins and/or minerals and edible oils once the capsules,gelcaps, caplets or other oral dosage forms dissolve, disintegrate orotherwise decompose, whether the composition is present in the form of asuspension, an emulsion or some other form, or in the form ofwater-soluble vitamins and/or minerals that have settled out from asuspension.

The following example describes and illustrates one of the compositionsof the present invention, and methods for preparing such compositions.This example is intended to be merely illustrative of the presentinvention, and not limiting thereof in either scope or spirit. Those ofskill in the art will readily understand that variations of certain ofthe conditions and/or steps employed in the procedures described in theexample can be used to prepare these compositions.

A mixture containing edible oils, fish oil and sunflower oil andsolid-state particles of vitamin B6, B9 and B12, with each of the threeB vitamins present in the form of a finely divided uniformly mixedpowder is prepared as follows. Sunflower oil is mixed with yellowbeeswax and heated to 145° F. causing the beeswax to melt. The mixtureof sunflower oil and melted beeswax is then transferred to a largervessel, where it is blended with lecithin. The beeswax and lecithin arepresent in quantities sufficient to enhance the ability of thesolid-state vitamins to remain at least temporarily in suspension. Thismixture is then blended into fish oil, including amounts of DHA and EPAsuch that the final mixture includes DHA in an amount which is about 50weight percent of the total weight of edible oils and EPA in an amountwhich is about 5 weight percent of the total weight of the edible oils.The mixture is allowed to come to approximately 80° F. Thereafter, thesolid-state particles of the vitamins are added to the blend of theedible oils and the beeswax and lecithin. This mixture is thoroughlyblended, at approximately 70° F., so as to assure content uniformity,and added to a hopper of a conventional soft-gel capsule, gelcap, orcaplet manufacturing device. Soft-gel ribbons are combined around unitdoses of the mixture to produce a semi-finished capsule, gelcap, orcaplet. Optionally ascorbyl palmitate may be added at the time thevitamin particles are added. It is also anticipated that the vitaminsmay or may not be coated at the time they are added to the mixture. Thevitamins may, for example, be coated with an edible oil, such asvegetable oil, prior to mixing. Furthermore, tocopherols or vitamin Emay optionally be added to the fish oil and vitamin B12 may betriturated with anhydrous ascorbic acid used as a diluent for thevitamin mixture.

To minimize oxidation of the fish oil and other edible oils that may beused in the invention, nitrogen may be used. For example, nitrogen maybe used to displace atmospheric oxygen in the head space within acontainer holding the oil. Also, a “nitrogen blanket” may be used as isknown to those of skill in the art to further minimize oxidation of theoil during the mixing stages and where it is otherwise being handled.Alternatively, the mixing could take place within a vacuum to minimizeoxidation of the oil.

In its raw form, gelatin is a thick, syrupy liquid. By the process ofcooling and manipulating, it is turned into a ribbon and laid out on asheet. This sheet is fed around the outer surfaces of two dyes androlled together. Two dyes in the shape of a soft gel rotate and cometogether. As they come together, the fill material from the hopper isinjected. Heat and pressure form the capsule, gelcap, or caplet into ahermetically sealed mold. The soft gels are very delicate when they comeoff the machine. A conventional drying process hardens them into thefinished product.

Prior to packaging, the gel capsules, gelcaps, or caplets (or other unitdosage form), may, optionally, be irradiated in order to killmicroorganisms that may have become be present therein or thereon duringproduction or otherwise. Such irradiation should be performed at alevel, and for a period of time, that does not diminish or destroy theeffectiveness of any of the edible oils or vitamins and/or mineralscontained therein.

The resulting gelatin capsules, gelcaps, caplets or other unit dosageforms may then be packaged in any manner known by those of skill in theart for packaging vitamins, minerals, oils pharmaceutical products orsimilar items.

Gel caps may be produced using known methods from a variety of differenttypes of gelatin, for example, type A gelatin, type B gelatin or gelatinthat is Kosher. Different types of gelatin can be obtained fromcommercial sources that are known by those of skill in the art, such asPost Apple Scientific (North East, Pa.), or be produced using knownmethods.

Gelatin is a protein that can be extracted using standard extractiontechniques from a product that results after a partial hydrolysis ofcollagenous raw material, which may be obtained from the skin, whiteconnective tissue, or bones of animals. For example, collagen, theprecursor of gelatin, can be pretreated for about 10-30 hours with a1-5% mineral acid for type A gelatin production or for about 35-90 daysin a liming process with a lime slurry for type B gelatin production.Type A gelatin exhibits the isoionic point at pH 7.0-9.5, whereas type Bgelatin, due to domination in the liming process, exhibits the isoionicpoint at 4.8-5.2. Type A gelatin can be manufactured from frozen orfresh edible-grade pig skins or from bone ossein. Most of type B gelatincomes from bones. While most edible gelatin is of type A, but type Bgelatin is also used. Pieces of bone generally are pretreated witheither mineral acid (for type A gelatin) or lime (for type B gelatin) inthe manner described above, and then demineralized in 4-7% hydrochloricacid for a period of about 7-14 days. The demineralized bone pieces thenundergo a standard liming procedure and the resulting materials arewashed, and subsequently subjected to about four or five extractions,which generally take from about 4 to 8 hours each, at increasedtemperatures, which generally range from about 131-212° F. The resultingextracts, which generally contain from about 3-7% gelatin, are thenfiltered, concentrated in a vacuum, evaporated, chilled, extruded asnoodles, and dried at a temperature generally ranging from about 86-140°F. The resulting dry gelatin can then be ground and blended to requiredor desired specifications.

Specific Preferred Embodiments

Other preferred embodiments of the compositions of the inventioncomprise specific combinations of two or more ingredients. Theseembodiments of the invention include, for example, the followingcombinations: (a) one fatty acid or other edible oil with one vitaminand/or mineral; (b) one fatty acid or other edible oil with more thanone vitamin and/or mineral; (c) two or more fatty acids or other edibleoils with one vitamin and/or mineral; (d) two or more fatty acids orother edible oils with two or more vitamins and/or minerals; or (e) anyof (a)-(d) optionally in combination with one or more other ingredientsthat are suitable for use in an oral pharmaceutical or other oral dosagecompositions, and that do not prevent, or substantially reduce, theeffectiveness of the compositions. Any one or more of the vitamins maybe in a solid state, a solubilized state, or some other state, andvarious compositions of the invention may include both solid stateand/or solubilized vitamins. In addition, The quantities of the one ormore fatty acids and/or other edible oils and vitamins and/or mineralsthat may be employed in these compositions need not be the same. Forexample, the compositions may contain a larger quantity of EPA than DHA(or other fatty acids), a larger quantity of DHA than EPA (or otherfatty acids), etc. As another example, the compositions may contain alarger quantity of one of the B vitamins, such as B6, B9 or B12, thananother B or other vitamin; or more vitamin B6 than either vitamin B9 orB12; or any combination thereof.

As further examples, compositions within the invention may include oneedible oil and vitamins B6, B9 and B12 (one edible oil and threedifferent B vitamins) more than one edible oil and any one vitamin B;more than one edible oil and vitamins B6, B9, and B12 (more than oneedible oil and three different B vitamins); or any combination thereof.

As still further examples, compositions within the invention may includeone or more edible oils, for example fish oil and/or sunflower oil, withvitamin C alone or in combination with B6, B9, and/or B12 admixedtherein, and with one or more oil soluble vitamins, for example vitaminA, dissolved in the fish oil or other edible oil. Other oil solublevitamins may be dissolved in the edible oil, including but not limitedto vitamins D, E, and K.

The compositions of the invention may also be in the form of anemulsion, such as a water-in-oil emulsion, an oil-in-water-in-oilemulsion, or the like, with at least one of the phases of the emulsionincluding the one or more vitamins and/or minerals suspended (ifsolid-state particles) or dissolved therein. For example, an“water-in-oil” emulsion is a mixture of two or more immiscible liquidsthat are generally held in suspension by one or more emulsifiers, and inwhich one or more oils constitutes the “continuous phase” and water oran aqueous solution is the “disperse phase.”

The compositions of the invention, in the form of emulsions, may beprepared using any edible emulsifier (any edible substance that aids inthe formation and/or maintenance of an emulsion), such as egg yolk oregg lecithin, and standard emulsification techniques and equipment knownby those of skill in the art. For example, water-in-oil emulsions maygenerally be formed by hand or mechanical stirring or whisking of thecontinuous and disperse phases of the emulsions for a period of time,and at a strength, that permits the aqueous phase to break down intodroplets, which are prefeiably small in size.

Other emulsions may be formed by slowly adding one or more ingredientsemployed in the compositions of the invention to one or more otheringredients while simultaneously mixing the ingredients rapidly. Thisdisperses and suspends tiny droplets of one liquid throughout anotherliquid. The two liquids would generally rapidly separate if anemulsifier were not added to the mixture. Emulsifiers generally functionas liaisons between two liquids and serve to stabilize the resultingmixture. Eggs and gelatin are among the foods that contain emulsifiers.Chemically, emulsions are colloids, heterogeneous mixtures composed oftiny particles suspended in another immiscible (unmixable) material.These particles are larger than molecules, but less than about oneone-thousandth of a millimeter (0.001 mm). Particles having such a sizegenerally do not settle out of an emulsion and can pass through filterpaper. The particles in a colloid can be solid, liquid or bubbles ofgas. The medium that they are suspended in can be a solid, liquid or gas(although gas colloids cannot be suspended in gas). Emulsions areliquid-liquid colloids, tiny liquid droplets suspended in anotherliquid. Emulsions are usually thick in texture and satiny in appearance.Microemulsions, which are special kinds of stabilized emulsions in whichthe dispersed droplets are extremely small (<100 nm), and which arethermodynamically stable, may also be used. A solid emulsion, which is acolloidal dispersion of a liquid in a solid, such as opal or pearl, mayalso be used.

Additional information concerning emulsification techniques, equipmentand ingredients that may be employed to prepare compositions of theinvention is present in S. Friberg et al., Food Emulsions (MarcelDekker, 3^(rd) Rev. Ex Ed., 1997), and in V. Vaclavik et al., Essentialsof Food Science (Kluwer Academic/Plenum Publishers, 2^(nd) Ed., 2003).

Packaging

The compositions of the invention are preferably packaged in a partiallyor totally opaque container. The package may include a label thatindicates how to administer the compositions, for example, the dailydosage, the dosing regimen, whether to take the composition with food oron an empty stomach, whether to avoid taking the composition withalcoholic beverages, etc.

All of the edible oils, other materials and equipment employed in theexample, and generally employed to make and use the compositions of thepresent invention, and to carry out the methods of the presentinvention, are commercially available from sources known by those ofskill in the art, such as Cargill, Incorporated (Minneapolis, Minn.),BASF Corp. (Mt. Olive, N.J.), RFI Ingredients (Blauvelt, N.Y.),Hoffmann-LaRoche Inc. (Nutley, N.J.), Martek Corp. (Columbia, Md.),Ocean Nutrition Canada, Ltd. (Bedford, Nova Scotia, Canada), PronovaBiocare AS (Lysakar, Norway), Napro AS (Brattvaag, Norway), DSM(Heerlen, NL), Berg Lipotech AS (Norway), ADM Food Oils (Decatur, Ill.),Oilseeds International, Ltd. (San Francisco, Calif.), and Post AppleScientific (North East, Pa.).

While the present invention has been described herein with somespecificity, and with reference to certain preferred embodimentsthereof, those of ordinary skill in the art will recognize numerousvariations, modifications and substitutions of that which has beendescribed which can be made, and which are within the scope and spiritof the invention. It is intended that all of these modifications andvariations be within the scope of the present invention as described andclaimed herein, and that the invention be limited only by the scope ofthe claims which follow, and that such claims be interpreted as broadlyas is reasonable.

Throughout this document, various books, patents, journal articles, websites, federal regulations and other publications have been cited. Theentireties of each of these books, patents, journal articles, web sites,federal regulations and other publications are hereby incorporated byreference herein.

1. A composition for an oral administration to a mammal comprising: (a)one or more water soluble vitamins or minerals, or combination thereof,in a combined amount that is effective for providing or enhancing anutritional, medical or other health benefit to the mammal, wherein theone or more water soluble vitamins or minerals are in a form that iscapable of being mixed with one or more edible oils; (b) one or moreedible oils in a combined amount that is effective for permitting theone or more water soluble vitamins or minerals to be mixed therewith;said one or more edible oils containing one or more omega-3 fatty acidsincluding DHA in a triglyceride form in an amount greater than about 50weight percent of the total weight of the omega-3 fatty acids; and,wherein the one or more water soluble vitamins or minerals are admixedwith the one or more edible oils and said composition is in a unitdosage form.
 2. The composition of claim 1 further comprising one ormore antioxidant agents in a combined amount that is effective forpreventing or reducing an oxidation, degradation or decomposition of theone or more water soluble vitamins or minerals or the one or more edibleoils, wherein the one or more antioxidant agents are admixed with theone or more water soluble vitamins or minerals and the one or moreedible oils.
 3. The composition of claim 1 where the water solublevitamins or minerals are coated with one or more edible oils and have anenhanced ability to travel through the stomach to the intestinal tractof the mammal without being degraded.
 4. The composition of claim 1further comprising oil soluble vitamins or minerals.
 5. (canceled) 6.The composition of claim 1, wherein the one or more of edible oilsincludes one or more additional fatty acids.
 7. The composition of claim6, wherein at least one of the one or more additional fatty acids is oneor more omega-3 fatty acid.
 8. The composition of claim 7, wherein theone or more additional omega-3 fatty acids is EPA or ALA, or combinationthereof.
 9. The composition of claim 1, wherein the composition includesone or more vitamins, and wherein at least one of the one or morevitamins is a B-vitamin.
 10. The composition of claim 9, wherein the oneor more B-vitamins is vitamin B6, vitamin B9 or vitamin B12, orcombination thereof.
 11. The composition of claim 1 wherein the watersoluble vitamins or minerals are in a form that is capable of being atleast temporarily suspended within the one or more edible oils.
 12. Acomposition for an oral administration by a mammal comprising: (a) oneor more solid-state particles of one or more water soluble vitamins orminerals in a combined amount that is effective for providing orenhancing a nutritional, medical or other health benefit to the mammal;(b) one or more edible oils that include one or more fatty acids,wherein the one or more fatty acids are omega-3 fatty acids, omega-6fatty acids or omega-9 fatty acids, said one or more omega-3 fatty acidsincluding DHA in a triglyceride form in an amount greater than about 50weight percent of the total weight of the omega-3 fatty acids, andwherein the one or more fatty acids are in a combined amount that iseffective for permitting the solid state particles to be at leasttemporarily suspended therein; wherein the solid state particles areadmixed with the one or more edible oils or at least temporarilysuspended therein and said composition is in a unit dosage form. 13.(canceled)
 14. The composition of claim 12 wherein the oral dosage formis a gelatin capsule.
 15. The composition of claim 12 further comprisingone or more antioxidant agents in an amount that is effective forpreventing or reducing an oxidation, degradation or decomposition of theone or more water soluble vitamins or minerals or the one or more edibleoils, wherein the one or more antioxidant agents are admixed with theone or more water soluble vitamins or minerals and the one or moreedible oils.
 16. The composition of claim 12 where the water solublevitamins or minerals are coated with one or more edible oils and have anenhanced ability to travel through the stomach to the intestinal tractof the mammal without being degraded.
 17. The composition of claim 12further comprising oil soluble vitamins or minerals.
 18. A compositionfor an oral administration to a mammal comprising: (a) one or moresolid-state particles of one or more water soluble vitamins, wherein theone or more water soluble vitamins are vitamin B6, vitamin B9 or vitaminB12, or a combination thereof, and wherein the one or more water solublevitamins are in a combined amount that is effective for providing orenhancing a nutritional, medical or other health benefit to the mammal;(b) one or more edible oils including one or more omega-3 fatty acids ina combined amount that is effective for providing or enhancing anutritional, medical or other health benefit to the mammal, said one ormore omega-3 fatty acids containing DHA in a triglyceride form in anamount greater than about 50 weight percent of the total weight of theomega-3 fatty acids, wherein the solid-state particles are mixed withthe one or more edible oils or at least temporarily suspended thereinand said composition is in a unit dosage form.
 19. (canceled)
 20. Thecomposition of claim 18 wherein the oral dosage form is a gelatincapsule.
 21. The composition of claim 18 wherein the one or more omega-3fatty acids includes EPA or ALA, or a combination thereof. 22.(canceled)
 23. (canceled)
 24. (canceled)
 25. The composition of claim 18wherein the composition includes Vitamin B9, and wherein the vitamin B9is in the form of L-5-methyltetrahydrofolate, (6S)-tetrahydrofolic acid,5 methyl-(6S)-tetrahydrofolic acid, 5 formyl-(6S)-tetrahydrofolic acid,10 formyl-(6R)-tetrahydrofolic acid, 5,10-methylene-(6R)-tetrahydrofolicacid, 5,10-methenyl-(6R)-tetrahydrofolic acid,5-formimino-(6S)-tetrahydrofolic acid, (6S)-5-methyltetrahydrofolic acidor polyglutamyl derivatives of tetrahydrofolate.
 26. The composition ofclaim 18 wherein the composition includes vitamin B12, and wherein thevitamin B12 is in the form of cyanocobalamin, cobalamin or cobalaminbound to recombinant intrinsic factor.
 27. The composition of claim 18wherein the composition includes vitamin B12 and wherein the vitamin B12is triturated with anhydrous ascorbic acid.
 28. The composition of claim18 wherein the vitamins are coated with an edible oil prior to mixingwith the one or more edible oils including one or more omega-3 fattyacids.
 29. The composition of claim 18 wherein an amount of one or moresuspending agents in a combined amount that is sufficient to provide orenhance an ability of the solid-state particles to remain, at leasttemporarily, in suspension is blended with one or more edible oils orcombination thereof.
 30. The composition of claim 29 wherein thesuspending agents are beeswax or lecithin, or a combination thereof. 31.The composition of claim 18 where the water soluble vitamins or mineralshave an enhanced ability to travel through the stomach to the intestinaltract of the mammal without being degraded.
 32. The composition of claim18 further comprising oil soluble vitamins or minerals or combinationthereof.
 33. The composition of claim 18 wherein vitamin B6 is includedin an amount ranging from about 1 mg to about 50 mg, vitamin B9 isincluded in an amount ranging from about 100 mcg to about 1000 mcg, andvitamin B12 is included in an amount ranging from about 200 mcg to about2000 mcg.
 34. A composition for an oral administration to a mammalcomprising: (a) one or more water soluble vitamins or minerals, orcombination thereof, in a combined amount that is effective forproviding or enhancing a nutritional, medical or other health benefit tothe mammal, wherein the one or more water soluble vitamins or mineralsare combined with an amount of water that is sufficient to form anaqueous solution; (b) one or more edible emulsifiers in a combinedamount that is effective to cause or enhance the formation of anemulsion, said one or more edible oils containing one or more omega-3fatty acids including DHA in a triglyceride form in an amount greaterthan about 50 weight percent of the total weight of the omega-3 fattyacids; (c) one or more edible oils in a combined amount that iseffective for forming an oil phase of an emulsion; wherein the aqueoussolution is combined with the one or more emulsifiers and the one ormore edible oils in a manner that forms an emulsion.
 35. (canceled) 36.The composition of claim 34 wherein the oral dosage form is a gelatincapsule.
 37. A method for preparing a composition for an oraladministration to a mammal comprising: (a) providing one or more solidstate particles of one or more water soluble vitamins or minerals, orcombination thereof; (b) providing one or more edible oils including oneor more fatty acids in a combined amount that is effective forpermitting the one or more water soluble vitamins or minerals to be atleast temporarily suspended therein; (c) optionally, mixing the one ormore water soluble vitamins or minerals, or combination thereof, for aperiod of time and under conditions that are sufficient to produce auniform mixture of the one or more water soluble vitamins or minerals,or combination thereof; (d) optionally, mixing the one or more edibleoils for a period of time and under conditions that are sufficient toproduce a uniform mixture of the one or more edible oils; (e)suspending, at least temporarily, an amount of the one or more watersoluble vitamins or minerals, or combination thereof, within an amountof the one or more edible oils, or combination thereof, that iseffective for producing a suspension of the solid-state particles of theone or more water soluble vitamins or minerals, or combination thereof,within the one or more edible oils, or mixtures thereof; (f) injecting aresulting suspension into an oral dosage form, wherein the oral dosageform is hard or soft capsule, gelatin capsule, caplet or gelatin caplet.38. The method of claim 37 wherein the one or more water-solublevitamins are vitamin B6, vitamin B9 or vitamin B12, or combinationthereof.
 39. The method of claim 38 wherein vitamin B9 is provided andwherein the vitamin B9 is in the form of L-5-methyltetrahydrofolate,(6S)-tetrahydrofolic acid, 5 methyl-(6S)-tetrahydrofolic acid, 5formyl-(6S)-tetrahydrofolic acid, 10 formyl-(6R)-tetrahydrofolic acid,5,10-methylene-(6R)-tetrahydrofolic acid,5,10-methenyl-(6R)-tetrahydrofolic acid,5-formimino-(6S)-tetrahydrofolic acid, (6S)-5-methyltetrahydrofolic acidor polyglutamyl derivatives of tetrahydrofolate.
 40. The method of claim38 wherein vitamin B12 is provided and wherein the vitamin B12 is in theform of cyanocobalamin, cobalamin or cobalamin bound to recombinantintrinsic factor.
 41. The method of claim 38 wherein vitamin B12 isprovided and wherein the vitamin B12 is triturated with anhydrousascorbic acid.
 42. The method of claim 37 wherein an amount of one ormore suspending agents in a combined amount that is sufficient toprovide or enhance an ability of solid-state particles to remain, atleast temporarily, in suspension is provided and wherein the one or moresuspending agents is blended with the one or more edible oils orcombination thereof.
 43. The method of claim 37 wherein the one or morefatty acids are omega-3 fatty acids, omega-6 fatty acids or omega-9fatty acids, or combination thereof.
 44. The method of claim 43 whereinthe one or more fatty acids are one or more omega-3 fatty acids orcombination thereof.
 45. The method of claim 44 wherein the compositionincludes one or more omega-3 fatty acids and wherein the one or moreomega-3 fatty acids are DHA, EPA or ALA, or combination thereof.
 46. Amethod for preparing a composition for an oral administration to amammal comprising: (a) providing one or more solid-state particles ofone or more water soluble vitamins or minerals or combination thereof;(b) mixing the solid-state particles in an amount of water that issufficient to form an aqueous solution; (c) providing one or more edibleemulsifiers or a combination thereof; (d) providing one or more edibleoils or combination thereof, including one or more fatty acids; (e)optionally, mixing the one or more edible oils or combination thereoffor a period of time and under conditions that are sufficient to producea uniform mixture of the one or more edible oils; (f) mixing the aqueoussolution with the one or more edible emulsifiers or combination thereofand the one or more edible oils or combination thereof under conditionsthat are sufficient to form an emulsion; (g) injecting the emulsion intoa hollow oral dosage form that is a soft or hard capsule, gelatincapsule, caplet or gelatin caplet.
 47. A method for enhancing thenutrition, health or medical condition of a mammal comprising: (a)providing an effective amount of a composition according to claim 1; (b)orally administering the effective amount of the composition accordingto claim 1 to a mammal.
 48. A method for enhancing the nutrition, healthor medical condition of a mammal comprising: (a) providing an effectiveamount of a composition according to claim 18; (b) orally administeringthe effective amount of the composition according to claim 18 to amammal.
 49. A method of lowering the serum cholesterol level of amammal, comprising administering to a mammal in need thereof aneffective cholesterol lowering amount of a composition comprising (a)one or more water soluble vitamins or minerals, or combination thereof,in a combined amount that is effective for providing or enhancing anutritional, medical or other health benefit to the mammal, wherein theone or more water soluble vitamins or minerals are in a form that iscapable of being mixed with one or more edible oils; (b) one or moreedible oils in a combined amount that is effective for permitting theone or more water soluble vitamins or minerals to be mixed therewith,said one or more edible oils containing DHA in an amount greater thanabout 50 weight percent of the total weight of the edible oils; and,wherein said DHA is present in a triglyceride form and the one or morewater soluble vitamins or minerals are admixed with the one or moreedible oils, and wherein said composition is in a unit dosage form. 50.A method of prevention of cardiovascular pathology in a mammal,comprising administering to a mammal in need thereof an effectivecardiovascular pathology preventative amount of a composition comprising(a) one or more water soluble vitamins or minerals, or combinationthereof, in a combined amount that is effective for providing orenhancing a nutritional, medical or other health benefit to the mammal,wherein the one or more water soluble vitamins or minerals are in a formthat is capable of being mixed with one or more edible oils; (b) one ormore edible oils in a combined amount that is effective for permittingthe one or more water soluble vitamins or minerals to be mixedtherewith, said one or more edible oils containing DHA in an amountgreater than about 50 weight percent of the total weight of the edibleoils; and, wherein said DHA is present in a triglyceride form and theone or more water soluble vitamins or minerals are admixed with the oneor more edible oils, and wherein said composition is in a unit dosageform.
 51. A method of reducing serum triglycerides in a mammal,comprising administering to a mammal in need thereof an effectivetriglyceride lowering amount of a composition comprising (a) one or morewater soluble vitamins or minerals, or combination thereof, in acombined amount that is effective for providing or enhancing anutritional, medical or other health benefit to the mammal, wherein theone or more water soluble vitamins or minerals are in a form that iscapable of being mixed with one or more edible oils; (b) one or moreedible oils in a combined amount that is effective for permitting theone or more water soluble vitamins or minerals to be mixed therewith,said one or more edible oils containing DHA in an amount greater thanabout 50 weight percent of the total weight of the edible oils; and,wherein said DHA is present in a triglyceride form and the one or morewater soluble vitamins or minerals are admixed with the one or moreedible oils, and wherein said composition is in a unit dosage form. 52.A method of lower serum low-density lipoproteins (LDL cholesterol) in amammal, comprising administering to a mammal in need thereof aneffective low-density lipoproteins (LDL cholesterol) lowering amount ofa composition comprising (a) one or more water soluble vitamins orminerals, or combination thereof, in a combined amount that is effectivefor providing or enhancing a nutritional, medical or other healthbenefit to the mammal, wherein the one or more water soluble vitamins orminerals are in a form that is capable of being mixed with one or moreedible oils; (b) one or more edible oils in a combined amount that iseffective for permitting the one or more water soluble vitamins orminerals to be mixed therewith, said one or more edible oils containingDHA in an amount greater than about 50 weight percent of the totalweight of the edible oils; and, wherein said DHA is present in atriglyceride form and the one or more water soluble vitamins or mineralsare admixed with the one or more edible oils, and wherein saidcomposition is in a unit dosage form.
 53. A method of increasing serumlevels of high-density cholesterol (HDL cholesterol) in a mammal,comprising administering to a mammal in need thereof an effectivehigh-density cholesterol (HDL cholesterol) increasing amount of acomposition comprising (a) one or more water soluble vitamins orminerals, or combination thereof, in a combined amount that is effectivefor providing or enhancing a nutritional, medical or other healthbenefit to the mammal, wherein the one or more water soluble vitamins orminerals are in a form that is capable of being mixed with one or moreedible oils; (b) one or more edible oils in a combined amount that iseffective for permitting the one or more water soluble vitamins orminerals to be mixed therewith, said one or more edible oils containingDHA in an amount greater than about 50 weight percent of the totalweight of the edible oils; and,wherein said DHA is present in atriglyceride form and the one or more water soluble vitamins or mineralsare admixed with the one or more edible oils, and wherein saidcomposition is in a unit dosage form.
 54. A method of lowering the serumcholesterol level of a mammal, comprising administering to a mammal inneed thereof an effective cholesterol lowering amount of a compositionof claim
 1. 55. A method of prevention of cardiovascular pathology in amammal, comprising administering to a mammal in need thereof aneffective cardiovascular pathology preventative amount of a compositionof claim
 1. 56. A method of reducing serum triglycerides in a mammal,comprising administering to a mammal in need thereof an effectivetriglyceride lowering amount of a composition of claim
 1. 57. A methodof lowering serum low-density lipoproteins (LDL cholesterol) in amammal, comprising administering to a mammal in need thereof aneffective low-density lipoproteins (LDL cholesterol) lowering amount ofa composition of claim
 1. 58. A method of increasing serum levels ofhigh-density cholesterol (HDL cholesterol) in a mammal, comprisingadministering to a mammal in need thereof an effective high-densitycholesterol (HDL cholesterol) increasing amount of a composition ofclaim 1.